For many years after its first description in 1924 thrombotic thrombocytopenic purpura was an intriguing puzzle for clinicians and researchers, not only for its unique pathology, perplexing changes in von Willebrand factor multimers and high rate of rapid fatality but also for its dramatic response to plasma infusion or exchange. The discovery of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat member 13) and its deficiency in thrombotic thrombocytopenic purpura, due to inhibitory autoantibodies or genetic mutations, provides a mechanistic scheme for understanding its pathogenesis.