There are three members of the steroid receptor coactivator (SRC) family of proteins: SRC1 (NCoA1), SRC2 (TIF2/GRIP1/NCoA2), and SRC3 (ACTR /TRAM1/AIB1). All SRC family members share significant structural homology and function to stimulate transcription mediated by nuclear hormone receptors and other transcriptional activators such as Stat3, NFκB, E2F1, and p53. Two SRC proteins, SRC1 and SRC3, function as histone acetyltransferases. In addition, all three family members can recruit other histone acetyltransferases (CBP/p300, PCAF) and histone methyltransferases (PRMT1, CARM1) to target promoters and cooperate to enhance expression of many genes. The SRC proteins play important roles in multiple physiological processes including cell proliferation, cell survival, somatic cell growth, mammary gland development, female reproductive function, and vasoprotection. SRC1 and SRC3 are conduits for kinase mediated growth factor signaling to the estrogen receptor and other transcriptional activators. Seven SRC1 phosphorylation sites and six SRC3 phosphorylation sites have been identified, which are induced by steroids, cytokines, and growth factors and involve multiple kinase signaling pathways. Research has shown that all three SRC family members are associated with increased activity of nuclear receptors in breast, prostate, and ovarian carcinomas. According to the literature, SRC3 is frequently amplified or overexpressed in a number of cancers, and SRC1/PAX3 and SRC2/MYST3 translocations are found associated with rhabdomyosarcoma and acute myeloid leukemia, respectively.