The studies of the cytochrome P450 (P450) arachidonic acid (AA) monooxygenase, now established as a major pathway for the bioactivation of AA, have uncovered new and important functional roles for this enzyme system in cell and organ physiology, and in the metabolism of endogenous substrate. Past and present advances in P450 biochemistry and molecular biology are beginning to provide a description of the P450 isoform specificity of AA bioactivation, and the mechanisms of action and physiological relevance of the P450 metabolites. Associations between genetically controlled alterations in P450 function, expression, or regulation and functionally meaningful phenotypes point to the critical roles played by the AA monooxygenase in the control of systemic blood pressure and the pathophysiology of hypertension.