The Great Gilly Hopkins, like most of Paterson's novels for young adults, addresses the difficulty of growing up in an unpredictable world where even friendship and family cannot be taken for granted. Eleven-year-old Gilly Hopkins has been left in foster care by her mother, Courtney. At the opening of the book Gilly has no friends, moving as she does from one foster home to another. Since her life seems to be controlled by a series of impersonal adults, she assumes a tough exterior to protect herself against further emotional pain. Her abusive behavior and rejection of friendly overtures keep others at a distance; she avenges her own pain by hurting others.

Emotional hardships cause Gilly, like many protagonists in Paterson's books, to gain a new understanding of herself and an appreciation of others. Gilly learns self-discipline, and she also realizes that her dreams are illusory. Even though she must face a tough reality, she finds love where she least expects it. Paterson always establishes hope and optimism even in her most bleakly realistic stories, which dramatize internal and external conflicts. At the conclusion of the novel, Gilly still faces difficult choices, but she knows herself better and is able to judge others more soundly. Paterson's well-drawn characters, who are thrust into emotionally taut situations, create a powerful narrative.