There are several themes in The Giant's House. They include:
- The burden of being a social outcast or person with disabilities living among conformists.
- Learning forgiveness and acceptance when people treat you poorly or differently.
- Realizing that love can transform people suffering from tragedy.
James Sweatt, a boy doomed to grown until he dies, and librarian Peggy Cort are outcasts in their small town. However, their love anchors them and helps them rise above the derision and isolation they face in their community. James is isolated by the disease that will kill him. Peggy is a social pariah misunderstood by people around her. Her deep love and commitment to James, however, helps her overcome the negative feelings about her neighbors. She dedicates her life to James, demonstrating true love, even when she knows their relationship cannot endure. Through James, Peggy is transformed by the power of love. She learns forgiveness and acceptance. Her love for him sustains her even after his death when she bears a child that she claims is his. Peggy is committed to keeping the giant's suffering, love, and compassion alive.