Love Medicine begins with June Morrissey freezing to death on her way home to the reservation. Although she dies at the beginning, the figure of June holds the novel together. Similarly, a love triangle among Lulu, Marie, and Nector is a link among the narratives, even though it is not a persistent theme in the novel. There is also a homecoming (or homing) theme in the novel. The use of multiple themes adds to the storytelling effect of the work. Other themes include: tricksters (in the Native American tradition), abandonment, connection to land, searching for identity and self-knowledge, and survival.

