Cytochrome P450 (CYP450) epoxygenase enzymes demonstrate organ and cell specific expression and each CYP450 enzyme isoform produces a distinct pattern of epoxyeicosatrienoic acids (EETs). Investigations are beginning to describe the regulation of specific tissue CYP450 epoxygenase isoforms that may be associated with alterations in organ function that occur during various physiological and pathophysiological states. The main biological actions of EETs are their ability to affect epithelial ion transport and vascular smooth muscle cell function. This chapter focuses on the organ localization and production of EETs and the action of EETs on epithelial and vascular smooth muscle cells.