Much of idiopathic thrombotic thrombocytopenic purpura (TTP) is attributed to the presence of an autoantibody to ADAMTS13, the metalloprotease that degrades ultralarge von Willebrand protein multimers. Most patients respond to treatment with therapeutic plasma exchange (TPE), which replaces the missing protease and removes the circulating inhibitor. However, a substantial fraction of idiopathic TTP cases (10%-20%) might not respond to TPE alone, and, therefore, interest has been gathering around the use of the novel immunosuppressive anti-B-cell antibody, rituximab. We report 2 cases of refractory TTP in which the combined use of plasma exchange and rituximab was associated with clinical resolution of active TTP, and we discuss the benefits and possible timing of combined therapy.