Studies of the cytochrome P450 arachidonic acid (AA) monooxygenase, now established as a major pathway for the bioactivation of this physiological important fatty acid, have uncovered new and important roles for this enzyme system in the regulation of kidney function, including renal hemodynamics and tubular ion transport. Associations between genetically controlled alterations in blood pressure and the activity and/or transcriptional regulation of the kidney Cyp2c AA epoxygenases and Cyp4a omega-hydroxylases revealed a role for these enzymes in the pathophysiology of hypertension, a leading cause of cardiovascular, cerebral, and renal morbidity and mortality. Furthermore, analysis of associations between genetic variants of human CYP4A11 and hypertension suggest a potential role for this gene as a determinant of polygenic blood pressure control in humans. These results are providing conceptually novel approaches for studies of the molecular basis of human hypertension that could lead to new strategies for the early diagnosis and clinical management of this devastating disease.