Continuing investigations of the roles of cytochrome P450 (CYP) arachidonic acid epoxygenase metabolites in the regulation of cardiovascular physiology and pathophysiology have revealed their complex and diverse biological effects. Often these metabolites demonstrate protective properties that are revealed during cardiovascular disease. In this regard, the epoxyeicosatrienoic acids (EETs) are an emerging target for pharmacological manipulation aimed at enhancing their cardiac and vascular protective mechanisms. This review will focus on the role of EETs in the regulation of vascular tone, with emphasis on the coronary circulation, their role in limiting platelet aggregation, vascular inflammation and EET contribution to preconditioning of the ischemic myocardium. Production and metabolism of EETs as well as their specific cellular signaling mechanisms are discussed.