The triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury is identified as hemolytic uremic syndrome (HUS). Complement activation is extremely active in HUS that is unusual. There have been reports of both hereditary and developed autoantibodies against the proteins that control complement. The lack of considerable mutation penetrance in all disease-causing genes demonstrates that a provoking event or trigger is necessary to disclose the complement regulatory failure. Prognosis is determined by the underlying genetic defect in both naturally occurring kidneys and kidneys that have undergone transplantation. Positive results from clinical trials using the complement inhibitor eculizumab to treat atypical HUS will impact how the condition develops.