The underlying pathological mechanism of thrombotic thrombocytopenic purpura (TTP) is the presence of microvascular thrombi that partially occlude the vascular lumins with overlying proliferative endothelial cells. Coombs-negative hemolytic anemia and severe thrombocytopenia owing to platelet clumping in the microcirculation are the most outstanding laboratory abnormalities. Classically, TTP has been recognized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, fever, and renal involvement, though only 20 to 40 percentage of patients will manifest the classic pentad. TTP remains a life-threatening disease the mortality rate of which may be as high as 90 percentage when untreated. Diagnosis is mainly based on hematological findings and a broad variety of neurological abnormalities, including ischemic or, less often, hemorrhagic stroke. Plasma exchange (PE) is currently the mainstay of treatment; however, rapid advances in the understanding of TTP pathophysiology may offer more specific and effective therapies in the near future.