Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal involvement. It causes end stage renal disease requiring dialysis in most affected patients. It mainly affects young adults (contrary to what was thought years ago). When aHUS is primary, the cause is a genetic mutation in the alternative complement pathway. Instead, secondary aHUS is caused by external factors that trigger the disease by themselves or in combination with a genetic vulnerability. The type of mutation determines the severity of the disease, prognosis, response to therapy and renal transplantation. Advances in the understanding of renal diseases associated with complement defects and the development of specific biologic therapies changed the course of this disease. Eculizumab is internationally approved for the treatment of primary aHUS. Its inhibitory action on the complement cascade leads to hematologic remission and restoration of renal function. We present a review of aHUS detailing its etiology, pathogenesis, clinical presentation, diagnosis and treatment.