Cerebral ischemia is one of the leading causes of death and disability in industrialized countries, with no curative treatments to date. Identification of potential targets and elucidation of their physiological role under stress conditions may give support to the development of drugs and strategies to contend with this pathology. In the last years, Heme oxygenase-1 (HO-1) has been considered by many groups as a potential target in ischemic damage. HO-1 is the enzyme responsible for the conversion of the heme group to billiverdin, carbon monoxide and iron; a highly regulated cytoprotective enzyme able to respond to numerous chemical or physical stressors, many of which decrease oxygen availability and generate oxidative stress. The disruption of HO-1 activity has been widely associated with a bad outcome in many disorders, and a protective role through its heme catabolism products has been observed in transplantation, cardiac ischemia, limb ischemia/reperfusion and different alterations that involve ischemia and reperfusion events. Here, we review recent reports supporting the protective role of HO-1 in cerebral ischemia. Results on the endogenous HO-1 response, overexpression of HO-1 and compounds that reduce ischemic damage through the induction of HO-1 in cerebral ischemia in in vivo and in vitro models are analyzed.