Soluble epoxide hydrolase (sEH) is an enzyme that contributes to metabolism of biologically active lipids including arachidonic acid epoxides (EETs). Soluble epoxide hydrolase inhibitors (sEHIs) were developed as a means to increase epoxides and sEHIs were found to reduce blood pressure, improve insulin sensitivity, and decrease inflammation. Further sEHI development led to clinical trials for hypertension and diabetes. More recently, there has been significant expansion of the potential clinical paths for sEHIs. This symposium will highlight possible clinical paths for sEHIs: 1) Chronic obstructive pulmonary disease (COPD), 2) Chronic kidney disease (CKD), 3) Neuropathic pain, Depression, and other CNS disorders.