ABSTRACTAs the largest receptor gene family in the human genome, with >800 members, the signal-transducing G protein-coupled receptors (GPCRs) play critical roles in nearly all conceivable physiological processes, ranging from the sensing of photons and odorants to metabolic homeostasis and migration of leukocytes. Unfortunately, an exhaustive review of the several hundred GPCRs expressed by myeloid cells/macrophages (P.J. Groot-Kormelink, L .Fawcett, P.D. Wright, M. Gosling, and T.C. Kent,BMC Immunol12:57, 2012,doi:10.1186/1471-2172-13-57) is beyond the scope of this chapter; however, we will endeavor to cover the GPCRs that contribute to the major facets of macrophage biology, i.e., those whose expression is restricted to macrophages and the GPCRs involved in macrophage differentiation/polarization, microbial elimination, inflammation and resolution, and macrophage-mediated pathology. The chemokine receptors, a major group of myeloid GPCRs, will not be extensively covered as they are comprehensively reviewed elsewhere.