Traditionally, PGD₂ has been considered to be a pro-inflammatory mediator, acting via classical PG receptors, such as the PGD₂ receptor (DP). PGD₂ is degraded rapidly in vitro and in vivo to a variety of metabolites, the majority of which were thought, until recently, to be physiologically inactive. Several “inactive” metabolites, particularly 15d-PGJ₂, have been shown to have wide-ranging effects on leukocytes and other cell types, however, and a potentially important anti-inflammatory role for PGD₂ has now been recognized, and the complexity of PGD₂ signaling is beginning to be elucidated. PGD₂ and its metabolites are biologically active over a broad concentration range, and, intriquingly, it appears that there are marked concentration-dependent variations in the consequences of signaling by these eicosanoids, which have the potential to exert pro- and anti-inflammatory effects. For example, the actions of PGD₂ can influence multiple stages in the life of the mature eosinophil, from causing its release from the bone marrow to inducing its recruitment and activation and, ultimately, regulating its apoptosis. This review is concerned with the diverse responses induced in leukocytes by PGD₂ and its metabolites and the signaling mechanisms which are thought to be responsible for them.