Prostaglandin D(2) (PGD(2)) is one of the most abundant lipid mediators present in the airways of asthmatics. However, little was known of the role it plays in the pathophysiology of asthma, until the identification of DP (DP1, PTGDR) and CRTH2 (DP2), two PGD(2)-specific transmembrane receptors with different distribution and intracellular signaling. Pharmacological tools, such as receptor-specific agonists and antagonists, and genetically-engineered mice, which lack either DP or CRTH2, have helped understand the complex effects of PGD(2) in allergic inflammation of the airways. Furthermore, genetic association studies have shown a positive linkage of the genetic polymorphisms in DP and CRTH2, with asthma phenotypes from specific ethnic backgrounds, further highlighting the importance of PGD(2) and its receptors in the pathophysiology of asthma.