Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme catabolism that converts heme to Fe++, carbon monoxide and biliverdin. HO-1 acts anti-inflammatory and modulates apoptosis in many pathological conditions. In transplantation, HO-1 is overexpressed in organs during brain death, when undergoing ischemic damage and rejection. However, intentionally induced, it ameliorates pathological processes like ischemia reperfusion injury, allograft, xenograft or islet rejection, facilitates donor specific tolerance and alleviates chronic allograft changes. We herein consistently summarize the huge amount of data on HO-1 and transplantation that have been generated in multiple laboratories during the last 15years and suggest possible clinical implications and applications for the near future.