Cardiovascular disease (CVD) is a human health crisis that remains the leading cause of death worldwide. The cytochrome P450 (CYP) class of enzymes are key metabolizers of both xenobiotics and endobiotics. Many CYP enzyme families have been identified in the heart, endothelium and smooth muscle of blood vessels. Furthermore, mounting evidence points to the role of endogenous CYP metabolites, such as epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraenoic acids (HETEs), prostacyclin (PGI(2)), aldosterone, and sex hormones, in the maintenance of cardiovascular health. Emerging science and the development of genetic screening have provided us with information on the differences in CYP expression among populations and groups of individuals. With this information, a link between CYP expression and activity and CVD, such as hypertension, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and cardiomyopathy and arrhythmias, has been established. In fact many currently used therapeutic modalities in CVD owe their therapeutic efficacy to their effect on CYP metabolites. Thus, the evidence for the involvement of CYP in CVD is numerous. Concentrating on treatment modalities that target the CYP pathway makes ethical sense for the affected individuals and decreases the socioeconomic burden of this disease. However, more research is needed to allow the integration of this information into a clinical setting.