Science and Technology
Relating the story of a mentally impaired man whose intelligence is increased through surgery and then lost, Flowers for Algernon touches on a number of literary themes. The most obvious of the novel's themes is the use and abuse of science and technology. The critic Mark R. Hillegas has identified Flowers for Algernon as the type of science fiction which deals with "problems imagined as resulting from inventions, discoveries, or scientific hypotheses"—in this case, a surgical procedure that can turn a person of subnormal intelligence into a genius. While the novel does not specifically take an anti-technology stance, it does make clear the limitations of technology as a "quick fix" to human problems—Charlie's operation is, ultimately, a failure in that he does not remain a genius. In a reversal of the classic notion of tragedy, the "flaw" which causes Charlie's downfall is not within him, but in the technology which sought to change him.

Knowledge and Ignorance
The idea that "there are some things humanity was not meant to know" may be traced in modern literature to Mary Shelley's novel Frankenstein (1818), and in some ways Flowers for Algernon contains echoes of Shelley's tale. The critic Thomas D. Clareson has directly connected Keyes's novel to Frankenstein in that Keyes combines the figures of the mad scientist and the "inhuman" creation into "the single figure of Charlie Gordon." This theme is further emphasized by the comments of Hilda, a nurse, and Fanny Birden, one of Charlie's coworkers, which compare his operation to the acquisition of forbidden knowledge in the Garden of Eden, which resulted in Adam and Eve being thrown out of Paradise.

However, Flowers for Algernon does not argue that humans should not try to attain knowledge, but rather that they should be conscious of the limitations of a purely intellectual approach to life. When Charlie buries himself in research to try to find the solution to the flaw in the operation, he declares, "I'm living at a peak of clarity and beauty I never knew existed." But later, during an argument with Professor Nemur, Charlie acknowledges that intelligence alone isn't enough: "intelligence and education isn't worth a damn … all too often a search for knowledge drives out the search for love."

Alienation and Loneliness
In an early "progress report," Charlie writes that he wants to be smart "so I can have lots of friends who like me." Unfortunately, once he becomes a genius, he discovers that there are a whole new set of problems that prevent him from establishing satisfactory relationships with other people. He has substituted one sort of alienation for another, as the condescension and cruelty he once faced from humanity has been replaced by misunderstanding, insensitivity, and fear. He falls in love with Alice Kinnian, the teacher who recommended him for the operation, but he realizes, "I am just as far away from Alice with an I.Q. of 185 as I was when I had an I.Q. of 70." Almost everything Charlie does in the novel is motivated by his desire to understand himself and establish functional relationships with others, perhaps most dramatically expressed when he wanders the streets of New York City by himself: "for a moment I brush against someone and sense the connection."

Atonement and Forgiveness
A major aspect of the novel is Charlie's efforts to understand and come to terms with the various people who have hurt him throughout his life: his mother, who physically and emotionally abused him; his father, who failed to defend him; his coworkers at the bakery, who brutalized him; the scientists who raised his intelligence but treated him like a laboratory animal. It is significant that when Charlie realizes the effects of the operation will not last, his major goal is to locate his family and establish some sort of peace with them. When he finally locates his mother, he tells himself, "I must understand the way she saw it. Unless I forgive her, I will have nothing." The tragedy of Charlie's fall from genius is relieved somewhat by the knowledge that he has come to terms with the people who mistreated him. In his last progress report, he writes, "If they make fun of you dont get sore because you remember their not so smart like you once thot they were."

Prejudice and Tolerance
Written during the height of the civil rights movement in the United States, Flowers for Algernon shows a profound concern with the rights of individuals to be treated as individuals, no matter what their condition in life. The early pages of the novel paint a grim portrait of how the mentally handicapped are treated, as Charlie is continually abused, verbally and physically, by his coworkers at the bakery. And when he becomes a genius, he is subject to a different sort of dehumanization, as the scientists in charge of the experiment regard him "as if I were some kind of newly created thing.... No one ... considered me an individual— a human being." This is perhaps most dramatically expressed when, witnessing a slow-witted boy being ridiculed for breaking dishes in a restaurant, Charlie lashes out at the customers: "Leave him alone! He can't understand. He can't help what he is … but for God's sake, have some respect! He's a human being!"

Sex
Although the novel is not primarily focused on sexual issues, a good deal of attention is paid to the fact that Charlie is sexually repressed as a result of an abused childhood. His mother, terrified that her "retarded" son would sexually assault his "normal" sister, violently repressed all normal displays of adolescent sexuality. The adult Charlie, once his intelligence has been raised to where he can understand the issues involved, initially has difficulty establishing a sexual relationship with Fay Lillman, a neighbor who seeks out his company, and is unable to have a physical relationship with Alice Kinnian, the woman he is in love with. Charlie's ability to have sex with Fay and, eventually, with Alice is seen as an important step in overcoming past traumas and becoming a fully functional adult.

In this story, which was the basis for the film Charly (1968), Charlie travels from ignorance to great intelligence and back again. Ironically, that same journey takes him from innocence to disillusionment to innocence recaptured. Charlie’s fleeting intellectual prowess carries an exorbitant price: an excruciating awareness of the cruelty that he has suffered at the hands of his coworkers. Charlie also finds pain in self-knowledge. He hides a picture of “the old Charlie Gordon” from himself in the hope of escaping the specter of his former illiteracy and childish naïveté, but he is haunted by the suspicion that he always saw—even through the veil of his dullness—his own isolating inferiority. He writes, “A child may not know how to feed itself, or what to eat, yet it knows of hunger.”

Charlie’s expanded intelligence fails to deliver the expected benefits. Although he delights in his newfound capacities for reading, memory, and logic, Charlie finds himself in a lose-lose situation with people. He writes on April 30: “The intelligence has driven a wedge between me and all the people I once knew and loved. Before, they laughed at me and despised me for my ignorance and dullness; now, they hate me for my knowledge and understanding.”

Fanny Girden, one of Charlie’s coworkers, invokes the Garden of Eden story from the Bible to explain the fear that Charlie’s intellect provokes: “It was evil when Eve listened to the snake and ate from the tree of knowledge. It was evil when she saw that she was naked. If not for that none of us would ever have to grow old and sick and die.” Charlie understands her message. His recognition of his coworkers’ attitudes toward him has made him feel naked and ashamed.

Through Charlie, Daniel Keyes probes societal attitudes toward the mentally handicapped. Charlie’s darkest hour comes at the peak of his intelligence, when he finds himself laughing along with everyone else at the clumsiness of a mentally handicapped boy. Charlie, unlike the others, becomes furious with himself for laughing and defends the boy: “He can’t help what he is! But for God’s sake . . . he’s still a human being.”

Keyes also questions the nature of friendship. As Charlie’s intelligence declines to its preoperative level, he concludes that because letting people laugh is a good way to make friends, he should have lots of friends in his new home.

The only true love demonstrated in the story is Charlie’s devotion to Algernon. He hates the mouse at first for winning all the races, but soon he develops an affection for the animal so intense that Algernon’s death evokes profound grief. Charlie’s friendship with Algernon grows from shared experience. He and the mouse face the same trials and endure the same painful outcomes. Keyes implies that the victories and defeats of life might link human beings in a similar way if only we could learn mutual trust and respect despite our differences.