Thrombotic microangiopathy (TMA) describes a spectrum of clinical syndromes all characterized by microvascular platelet thrombi with resultant thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Organ dysfunction can commonly include renal failure or neurologic abnormalities such as mental status changes, confusion, or seizures. The most common TMA is idiopathic thrombotic thrombocytopenic purpura (TTP). Hemolytic-uremic syndrome (HUS) is commonly used to describe a TMA with associated renal insufficiency, and typically without neurologic sequelae. The distinction between TTP and HUS is not always clear, and therefore HUS can be reserved for the distinct TMA syndrome associated with bloody diarrhea due to shiga-toxin producing Eschericia coli 0157.H7. There are a variety of other conditions which can also be associated with a TMA including pregnancy, autoimmune diseases, cancers, drug-associated TMA and TMA associated with hematopoietic stem cell or solid organ transplantation. The diagnosis of TTP should be reserved for idiopathic cases, while the term TMA should be utilized for the many secondary causes of the syndrome.