The cardiovascular effects of epoxyeicosatrienoic acids (EETs) include vasodilation, antimigratory actions on vascular smooth muscle cells and anti-inflammatory actions. These endogenous lipid mediators are broken down into diols by soluble epoxide hydrolase (sEH), and so inhibiting this enzyme would be expected to enhance the beneficial cardiovascular properties of EETs. sEH inhibitors (sEHIs) that are based on 1,3-disubstituted urea have been rapidly developed, and have been shown to be antihypertensive and anti-inflammatory, and to protect the brain, heart and kidney from damage. Although challenges for the future exist — including improving the drug-like properties of sEHIs and finding better ways to target sEHIs to specific tissues — the recent initiation of the first clinical trials of sEHIs has highlighted the therapeutic potential of these agents.