Signaling lymphocytic activation molecule (SLAM) family receptors mediate important regulatory signals in immune cells, as a result of their exquisite ability to associate with members of the SLAM-associated protein (SAP) family of adaptors. As discussed herein, recent findings show that the SLAM and SAP families carry out pivotal functions in innate-like and conventional lymphocytes. They are critically needed for the development of innate-like lymphocytes such as NKT cells. In addition, they influence several of the functions of conventional lymphocytes, including the ability of CD4⁺ T cells to secrete certain cytokines and mediate B cell help; CD8⁺ T cell proliferation and cytokine production; NK cell-mediated cytotoxicity; and B cell antibody production. These unique functional properties appear to be facilitated by the ability of SLAM-related receptors to serve as self-ligands during homotypic interactions between immune cells. The importance of the SLAM-SAP pathway in normal immunity is highlighted by the finding that SAP is mutated in humans suffering from the immunodeficiency X-linked lymphoproliferative disease.