Prostaglandin D2 (PGD2) is one of the most abundant arachidonic acid metabolites produced by mast cell cells and Th2 lymphocytes and has been detected in elevated concentrations in a number of allergic conditions. PGD2 has the ability to mimic a number of the key features of allergic disease including the vascular effects leading to erythema and oedema and effects on Th2 lymphocytes, eosinophils and basophils leading to their recruitment and activation. It is well established that the vasodilator of properties of PGD2 are mediated by DP1 while the ability of PGD2 to promote chemotaxis of Th2 lymphocytes, eosinophils and basophils has more recently to been discovered to be due to an action on chemoattractant-homologous receptor expressed on Th2 cells (CRTH2, also known as DP2)(Hirai et al 2001). Mast cells play a central role in orchestrating the pathophysiological changes that occur in allergic disease including influencing the characteristic pattern of Th2 lymphocyte recruitment and activation that is associated with the late phase allergic response. It is of interest, therefore, that the ability of supernatants from immunologically activated mast cells to promote chemotaxis of Th2 lymphocytes is mediated by CRTH2(Gyles et al, 2006) as is the production of the Th2 cytokines interleukin 4, 5 and 13 in response to PGD2(Xue et al, 2005). CRTH2 may also contribute to mast cell independent activation of Th2 cells since CRTH2 antagonists inhibit the ability of supernatants from activated Th2 cells to stimulate chemotactic activation of naïve Th2 cells (Vinall et al, 2007). Interestingly, PGD2 can also inhibit the production of cytokines such as interleukin 12 by dendritic cells, an effect mediated by DP1 which in some settings may promote an environment where polarisation of Th0 to Th2 cells is favoured. Therefore, based on these observations it is proposed that the concerted action of DP1 and CRTH2 plays a fundamental role in the polarization of T cells to the Th2 phenotype and their subsequent recruitment and activation at sites of allergic inflammation. In vivo pharmacological studies with recently discovered antagonists combined with genetic analysis support the view that these receptors play a pivotal role in mediating these aspects of allergic disease that are resistant to current therapy.