Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that most often arises from inhibition of the enzyme ADAMTS13 by autoantibodies. This provides the rationale for the use of rituximab, an anti-CD20 monoclonal antibody, as an effective treatment. Multiple reports have indicated success employing it in patients with TTP, but only a few have reported its use during remission as a prophylaxis to prevent a relapse. Herein, we report the case of a patient with chronic relapsing TTP who was successfully treated with prophylactic rituximab. We also provide a review of the literature on this topic.