It has been 40 years since the discovery of Fcγ receptors (FcγRs) and their function. FcγRs regulate a variety of immune responses, including phagocytosis, degranulation, antibody-dependent cellular cytotoxicity, transcriptional regulation of cytokines, chemokine expression, B-cell activation, and immune complex clearance. It is well known that FcγRs serve as a critical link between the humoral and cellular branches of the immune system and play an important role in many conditions, including infection, cancer, and autoimmune diseases. Recent studies suggest that FcγR polymorphisms influence efficacy and side effects of monoclonal antibody-based immunotherapy, which might provide a useful prognostic marker for treatment in the future. Rituximab has been proven effective in treating patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Some FcγR genotypes correlate with rituximab efficacy in patients with NHL but not in patients with CLL. In this review, FcγR function and the association between FcγR polymorphisms and rituximab efficacy in NHL and CLL are discussed.