Heme oxygenase-1 (HO-1) is a cytoprotective protein whose expression is consistently associated with therapeutic benefits in a number of pathologic conditions such as atherosclerotic vascular disease and inflammation. Although the expression of HO-1 in most tissues is low, a large number of clinical and experimental pharmacologic compounds have been demonstrated to induce HO-1. This induction is suggested to be at least partially responsible for the perceived therapeutic efficacy of these compounds. The increase in HO-1 expression in response to these compounds is the result of a complex regulatory network involving many signaling pathways and transcription factors. Understanding both the pathways by which HO-1 is induced and the mechanism through which the enzyme exerts its beneficial effects may facilitate the development of novel drugs.