Suppressor of cytokine signaling (SOCS) family proteins were initially identified as inhibiting cytokine signaling pathways through a negative feedback loop involving the inhibition of Janus kinase activity. More recent data suggest that SOCS proteins may also modulate signaling mediated through receptor tyrosine kinases. Krebs and Hilton discuss research implicating SOCS-1 and SOCS-3 as inhibitors of insulin receptor-mediated and insulin-like growth factor-1 receptor-mediated signaling pathways, as well as the increasing evidence that SOCS proteins may act in part by participating in a ubiquitin ligase complex to promote the degradation of target proteins.