When activated by diverse stimuli, mast cells mobilize arachidonic acid through cytosolic phospholipase A2, and rapidly generate both prostaglandin D2 and leukotriene C4, the parent molecule of the cysteinyl LTs. While initially recognized for their bronchoconstricting and vasoactive properties, these two eicosanoids are now known to serve diverse and pivotal functions in effector cell trafficking, antigen presentation, immune cell activation, matrix deposition, and fibrosis. This chapter reviews the biological functions for each eicosanoid and their respective receptor classes, discusses the mechanisms by which the generation of eicosanoids by mast cells is regulated, and considers the potential pathobiologic and therapeutic ramifications in host defense, inflammation, and allergic diseases.