Epoxide hydrolases are a group of enzymes that convert the epoxide group of chemical compounds to corresponding diols by the addition of water. Soluble epoxide hydrolase (sEH, formerly referred to as cytosolic epoxide hydrolase), which is widely distributed in mammalian tissues, is the primary enzyme responsible for the conversion of epoxyeicosatrienoic acids (EETs), the bioactive lipid mediators formed from arachidonic acid by cytochrome P450 epoxygenase, to their corresponding diols. EETs, but not their diols, are endogenous anti-hypertensive eicosanoids. Disruption of the sEH gene in male mice decreases blood pressure, and inhibition of sEH decreases blood pressure in several experimental hypertensive models. Potent selective sEH inhibitors have been developed, and these sEH inhibitors have potential to become a novel class of anti-hypertensive drug.