The story is recounted by the protagonist, Will, in an amiable, conversational fashion, with frequent flashbacks to earlier portions of his life.

In the novel, Medicine River, Thomas King creates a story of a little community to reflect the whole native nation.

Medicine River shows the history of Canada and teaches readers to learn from the past experience in order to become better people.

Will meets Louise who becomes an unfulfilled love interest that very much represents Will's existence, a series of half-fulfilled expectations.

One advisor writes, "It is a humorously told 'homecoming novel' that echoes an oral storytelling style, yet at the same time, debunks any kind of stereotypical 'cultural voice.'