Steroid receptor coactivator (SRC) family members (SRC-1, SRC-2, SRC-3) interact with nuclear receptors (NRs) and many transcription factors to enhance target gene transcription. Deregulation of SRCs is widely implicated in NR mediated diseases, especially hormone dependent cancers. By integrating steroid hormone signaling and growth factor pathways, SRC proteins exert multiple modes of oncogenic regulation in cancers and represent emerging targets for cancer therapeutics. Recent work has identified SRC-targeting agents that show promise in blocking tumor growth in vitro and in vivo, and have the potential to function as powerful and broadly encompassing treatments for different cancers.