Signal transduction via cytokine receptors is regulated by several mechanisms that control initiation, magnitude and duration of the signaling pathways. Cytokine-induced SOCS family adaptors function as feedback inhibitors of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. Specific gene-targeted mice have unveiled critical, non-overlapping functions for SOCS1 and SOCS3 in lymphocyte development and homeostasis, and in the regulation of macrophage and dendritic cell functions. In this review, we will discuss the structure of SOCS proteins, mechanisms by which they control the JAK-STAT pathway and their role in immune regulation.