Prostaglandin E 2 (PGE 2 ) is the most abundant eicosanoid and a very potent lipid mediator. PGE 2 is produced predominantly from arachidonic acid by its tightly regulated cyclooxygenases (COX) and prostaglandin E synthases (PGES). Secreted PGE 2 acts in an autocrine or paracrine manner through its four cognate G protein coupled receptors EP1 to EP4. Under physiological conditions, PGE 2 is key in many biological functions, such as regulation of immune responses, blood pressure, gastrointestinal integrity, and fertility. Deregulated PGE 2 synthesis or degradation is associated with severe pathological conditions like chronic inflammation, Alzheimer's disease, or tumorigenesis. Therefore, pharmacological inhibition of COX enzymes and PGE 2 receptor antagonism is of great therapeutic interest.