The signalling lymphocytic activation molecule (SLAM) family of receptors is expressed by a wide range of immune cells. Through their cytoplasmic domain, SLAM family receptors associate with SLAM-associated protein (SAP)-related molecules, a group of cytoplasmic adaptors composed almost exclusively of an SRC homology 2 domain. SAP, the prototype of the SAP family, is mutated in a human immunodeficiency named X-linked lymphoproliferative (XLP) disease. Recent observations indicate that SLAM family receptors, in association with SAP family adaptors, have crucial roles during normal immune reactions in innate and adaptive immune cells. The latest progress in this field is reviewed here.