Leukocyte Fcγ receptors (FcγR) confer potent cellular effector functions to the specificity of IgG. FcγR‐induced leukocyte functions, including antibody‐dependent cellular cytotoxicity, phagocytosis, superoxide generation, degranulation, cytokine production and regulation of antibody production, are essential for host defense and immune regulation. The efficacy of IgG‐induced FcγR function displays inter‐individual heterogeneity due to genetic polymorphisms of three FcγR subclasses, FcγRIIa (CD32a), FcγRIIIa (CD16a), and FcγRIIIb (CD16b). FcγR polymorphisms have been associated with infectious and autoimmune disease, or with disease severity. FcγR polymorphisms may furthermore serve as markers for therapeutic efficacy and side‐effects of treatment with monoclonal antibodies. In this review, FcγR function and the relevance of FcγR polymorphisms as prognostic markers for inflammatory disease and antibody‐based immunotherapy are discussed.