Allotransplantation is the preferred means of organ replacement; however, application is limited by a severe shortage of human organ donors. Several alternate approaches to treat organ failure are under exploration. These approaches include development of artificial organs, cellular transplants, organogenesis and xenotransplantation. The feasibility of each approach may be limited by physical, biochemical, and immunologic obstacles. Here we consider how each approach, either alone or in conjunction with other approaches, may be used to replace or supplement the function of diseased or injured human organs.