Epoxyeicosatrienoic acids (EETs) generated from arachidonic acid by cytochrome P450 (CYP) epoxygenases have beneficial effects in certain cardiovascular and kidney diseases. Hence, great efforts have been made to develop drugs targeting the EET pathway. Some of these agents are currently under evaluation in clinical trials for treatment of hypertension and diabetes. In this issue of the JCI, Panigrahy et al. evaluate in a systematic way the role of CYP epoxygenases and the metabolites they generate in cancer progression. Their findings, along with previous studies, raise concerns about using these drugs in humans.