The well-established physiological function of erythropoietin (EPO) is the induction of erythropoiesis. A growing body of evidence indicates that EPO has tissue-protective effects and prevents tissue damage during ischemia and inflammation. Tissue protection after ischemia and injury has been found in the brain, heart, and kidney. It has been speculated that EPO has anti-apoptotic effects in cardiovascular cells. These novel effects of EPO seem to be independent of its erythropoietic activity. Unclear is the role of the known EPO receptor or whether other signaling pathways are involved; a novel EPO receptor might be involved in tissue protection by this hormone. This review article summarizes present knowledge of cardiovascular and renal protective effects of EPO and discusses possible underlying mechanisms.