Thrombotic microangiopathies are rare disorders characterized by the concomitant occurrence of severe thrombocytopenia, microangiopathic hemolytic anemia, and a variable degree of ischemic end organ damage. The latter particularly affects the brain, the heart and the kidneys. The primary forms, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), although in their clinical presentation often overlapping, have distinctive pathophysiologies. TTP is the consequence of a severe ADAMTS13 deficiency, immune-mediated due to circulating autoantibodies (iTTP), or caused by mutations in the ADAMTS13 gene (cTTP). HUS develops following an infection with Shiga-toxin producing bacteria (STEC-HUS), or as the result of excessive activation of the alternative pathway of the complement system because of mutations in genes of complement system proteins in atypical HUS (aHUS). This article is protected by copyright. All rights reserved.