Thrombotic microangiopathy is characterized by hemolytic anemia, thrombocytopenia, and visceral disorders associated with the formation of thrombi in the microcirculation vessels. They are rare, with an incidence of 6–8 cases/million inhabitants per year. The best known form of thrombotic microangiopathy is the thrombotic thrombocytopenic purpura, characterized by brain damage, thrombocytopenia, and hemolytic uremic syndrome with severe renal impairment. A syndrome of thrombotic microangiopathy can also be observed in some contexts such as cancer, infection by the human immunodeficiency virus, transplantation, or pregnancy. The microangiopathies are severe diseases, but their prognosis can be excellent if they are quickly diagnosed and properly treated. This underlines the crucial role of emergency physicians. Progress during the recent years in understanding the physiopathology indicates some ways of targeted therapeutic that should further improve the prognosis of the disease.