Hypertension is a well established risk factor for cardiovascular diseases such as stroke and is the leading cause of chronic kidney failure. Although a number of pharmacologic agents are available for the treatment of hypertension including agents that affect the renin-angiotensin-aldosterone system (RAAS), unmet needs in the treatment of hypertension suggest that identification of novel pharmacological targets would be an important healthcare goal. One potential target is prostaglandin E(2) (PGE(2)), a potent lipid mediator with a diverse and sometimes opposing range of biological effects. PGE(2) signals through four subtypes of G-protein coupled receptors designated EP1 through EP4. PGE(2) functions primarily as a vasodepressor; under certain conditions PGE(2) administration mediates vasopressor activity. This review focuses on the current understanding of the roles of PGE(2) receptors in vascular reactivity, hypertension and end-organ damage.