Thrombotic microangiopathy results from thrombotic occlusion of the microvasculature leading to fragmentation of red blood cells, profound thrombocytopenia, and a microangiopathic hemolytic anemia with elevation of lactate dehydrogenase and negative direct Coomb’s test. This constellation of clinical and laboratory findings is not due to one disease entity; rather, it represents a variety of underlying diagnoses. Among the major disease entities are TTP/HUS, which can be congenital or acquired, bacterial infections, medications, vascular or endothelial pathology like Kasabach-Merritt phenomenon, and stem cell transplantation. In this paper, we offer a review of some of the major causes of thrombotic microangiopathy.