The physiopathology of thrombotic thrombocytopenic purpura (TTP) has been clarified since 1998, when it was shown that TTP in adults was most often associated with an acquired deficiency of von Willebrand factor-cleaving protease (ADAMTS13) due to autoantibodies, whereas TTP in children was most often associated with a hereditary autosomal recessive severe deficiency of ADAMTS13. The hereditary form of TPP (Upshaw-Schulman syndrome) is a very rare but life-threatening disease if adequate treatment (plasma therapy) is not administered. First manifestations occur before age 10 in two thirds of cases and as soon as birth in most cases. The subsequent course is characterized by recurrent hemolytic and thrombocytopenic crises, with intervals between relapses from every 3 to 4 weeks in two thirds of cases to several months or years in one third of cases. TTP crises are associated with cerebral vascular accidents in at least 30% of patients, with a risk of neurologic sequelae in approximately 20% of patients. Renal involvement includes frequent acute renal failure due to hemoglobinuria and/or thrombotic microangiopathy during hemolytic crisis and progressive renal deterioration in approximately 50% of cases, leading to chronic or end-stage renal failure in approximately 20% of patients. The clinical phenotype may vary from the typical congenital recurrent TTP. Some mild forms are limited to a fluctuating thrombocytopenia and may be misdiagnosed as idiopathic thrombocytopenic purpura. Phenotypic variability may be observed within a single family, which suggests a role of modifier genes. Fresh frozen plasma (FFP) replaces active ADAMTS13. Ten milliliters per kilogram FFP every 2 to 4 weeks suffices to maintain remission. FFP infusions are best used preventively, given that rescue infusions may not prevent central nervous system and renal involvement. It is hoped that plasmatic or recombinant purified ADAMTS13 will be available in the years to come.