The main theme of Milkweed is identity. The quest to define one's identity is a natural part of adolescence. For Misha, however, the task is even more vexing as he has no idea where he came from or who he is. Misha's search for an identity to call his own converges with the Holocaust, when one's identity determined whether one lived or died. Misha recollects, "And so, thanks to Uri, in a cellar beneath a barbershop somewhere in Warsaw, Poland, in the autumn of the year nineteen thirty-nine, I was born, you might say." When Uri bestows upon him his identity and the fabricated story of his family, Misha clings desperately to each detail; when he sees horses, he actually looks for Greta, his fictitious favorite horse. Misha is "reborn" as Jack Milgrom by a disaffected immigration official upon his arrival in the United States after the war. However, it seems as though he does not have a true identity to call his very own until his granddaughter, Wendy Janina, affectionately refers to him as "Poppynoodle."

Survival is another key theme throughout Milkweed. During the Holocaust, people were willing to do virtually anything it took to stay alive. Some resorted to eating pigeons, squirrels, and dogs, while others relied on stealing. Such was the case with Misha; he was a spry, nimble thief who was able to steal what he needed to stay alive. What separated Misha from others, however, was that he always shared his loot with others; Misha was a source of sustenance for Janina and her family as well as for Uri and the other boys. This quality also gives readers insight into his character; despite the fact that Misha has always had to fend for himself, somewhere along the way he learned the importance of sharing. Another survival strategy for those in the novel was remaining invisible. Although intellectually Misha knew the importance of this (as instructed by Uri), he seems almost unwilling to hide. It is as though his flagrant behavior was the result of his "birth"; perhaps he was so happy to have an identity and to belong to a group that he could not contain his delight.

Another theme inherent in Milkweed is that of childhood innocence. It is as if Misha's naivete and innocence were a critical part of his survival. He seemed not to realize the severity of what was happening around him. Whereas everyone was on edge about Himmler's arrival in and tour of the ghetto, Misha saw him for what he was: a man with a bad moustache who looked like Janina's Uncle Shepsel. When readers get a glimpse into Misha's post-war life, it is as if he has never grown up or matured. One has the sense that "Poppynoodle" is on the same level intellectually as Wendy. Innocence may have been a defense mechanism for Misha; perhaps if he had acknowledged the horrors taking place around him, he would have lost his wits and been caught.

The novel's title, Milkweed, is also a recurring theme. When one thinks of milkweed, what comes to mind is the plant. It is an incredibly resilient plant, growing as heartily in the fall as it does in the spring. It also serves as the primary food source for the beautiful monarch butterfly, which cannot grow without it. So in many ways, Misha is the personification of milkweed. Through his rampant stealing he is able to nourish himself, Uri, and the boys as well as Janina and her family. No matter how difficult times become, like the milkweed, Misha perseveres. However, despite its many strengths, milkweed is also transient and fleeting once its silk is caught by a breeze.