15-Deoxy-Delta-12,14-prostaglandin J2 (15d-PGJ2) is the most recently discovered prostaglandin. This cyclopentanone, the dehydration end product of PGD2, differs from other prostaglandins in several respects. There is no specific prostaglandin synthase (PGS) leading to 15d-PGJ2 production and no specific 15d-PGJ2 receptor has been identified to date. Instead, 15d-PGJ2 has been shown to act via PGD2 receptors (DP1 and DP2) and through interaction with intracellular targets. In particular, 15d-PGJ2 is recognized as the endogenous ligand for the intranuclear receptor PPARgamma. This property is responsible for many of the 15d-PGJ2 anti-inflammatory functions. In this review, we summarize the current understanding of 15d-PGJ2 synthesis, biology and main effects both in molecular physiology and pathological states.