The stress protein heme oxygenase-1 (HO-1) has been suggested to play an important role in cellular defense against injury. This protein is expressed in many tissues during inflammatory disorders and it could be considered as an adaptive mechanism in physiological and pathological processes. HO-1 participates in the regulation of vascular tone, leukocyte activation and adhesion, cytokine production, iron levels or apoptosis, resulting in the protective effects observed in animal models of inflammation. We have studied the signaling mechanisms involved in HO-1 regulation in several cell types, as well as the contribution of inflammatory mediators to this response. Therefore, HO-1 is a potential therapeutic target and modulation of this protein may be useful for the treatment of inflammatory and degenerative conditions.