Subfamily A5 of the GPCRs consist of seven members of receptors that are activated by either neuropeptides or leukotriene-derivatives (galanin, leukotrienes and cysteinyl leukotrienes, relaxin, melanin, urotensin, and kisspeptin (a.k.a. metastin). The cysteinyl leukotrienes (cys-LTs) are a family of potent bioactive lipids that act through two structurally divergent GPCRs, termed the CysLT1 and CysLT2. Their endogenous ligands are LTC4, LTD4, and LTE4 are peptide-conjugated lipids that are prominent products of activated eosinophils, basophils, mast cells (MCs), and macrophages. These leukotrienes are commonly recognized as potent inflammatory mediators that initiate and propagate a diverse array of biologic responses. Consequently, clinically efficacious receptor antagonists and inhibitors of cys-LT synthesis have been introduced to treat asthma, immune responses, inflammation, tissue repair, and fibrosis.