Thrombotic thrombocytopenic purpura is an uncommon disease that often presents with a striking and acute clinical picture. Although first described more than 80 years ago, the therapy has changed little since the discovery that plasma, and then plasma exchange, could bring about a remarkable response, changing survival rates from 20% to more than 80%. However, although plasma exchange is now considered the standard of care, there is still considerable discussion concerning the appropriate schedules for therapy and the types of fluids that should be used. Because plasma exchange (PE) is not effective in all patients, and at least 30% of patients will have one or more relapses, several adjuvant therapies have also been used. Most recently, this has included the use of rituximab to achieve an immunomodulatory effect.