The human soluble epoxide hydrolase (sEH; EC 3.3.3.2) is the product of the EXPH2 gene. The sEH catalyzes the addition of a water molecule to an epoxide, resulting in the corresponding diol. Early work suggested a role of sEH in detoxifying a wide array of xenobiotic epoxides; however, recent findings clearly implicate the sEH in the regulation of blood pressure, pain, and inflammation through the hydrolysis of endogenous epoxy fatty acids such as epoxyeicosatrienoic acids (EETs). Both expression and activity of sEH are influenced by a wide array of xenobiotics, underlying how environmental contaminants could influence human health through sEH. This unit describes radiometric, fluorimetric, and mass spectrometric assays for measuring the activity of sEH and its inhibition.