As the protagonist of Regeneration, Rivers undergoes a personal growth that forms the foundation for the structure of the story. This character is loosely based on the real W.H.R. Rivers, who worked as a psychiatrist at Craiglockhart from 1916–1917 and served as a treating physician for Siegfried Sassoon. Like the character, the real Rivers had a stammer that he sometimes found difficult to control, though his father was a speech therapist. Rivers studied anthropology and went on several expeditions before returning to Cambridge to do research on nerve regeneration with a friend, Henry Head. At Craiglockhart, Rivers officially treated Sassoon for an "anti-war complex." The real Rivers writes about Sassoon under the alias "Patient B" in his book Conflict and Dreams.

Though Rivers the character is based upon the real Dr. Rivers, Barker's accounts of his discussions, thoughts, and moral dilemmas are entirely fictional. In the novel, Rivers is a dynamic character who develops and changes throughout the work—ironic, since it is his job to change others. With a traditional Victorian education and a strong belief in honor, Rivers feels bound to his duty to heal men so they may return to war. Rivers is not close-minded, however; in fact, his deep sympathy for the suffering of his patients causes him to rethink previously solid beliefs. He feels a deep conflict about whether he is doing the right thing by treating men just so that they can return to war and be killed. Furthermore, Rivers feels guilty over the level of control and influence he has over his patients. After watching Dr. Yealland's method of electro-shock therapy, Rivers wonders how much he really differs from his harsh colleague. The novel charts Rivers's slow journey of realization and growing doubtfulness about the justification for the death of an entire generation.