Many, if not most, cytokines important for immune responses utilize the Jak-STAT signaling pathway. Jaks are receptor-associated protein tyrosine kinases, and STATs are latent cytoplasmic transcription factors that are activated by tyrosine phosphorylation. STATs play critical, nonredundant roles in mediating cellular transcriptional responses to cytokines, and in cell activation, survival and proliferation. The roles of Jaks and STATs in immune responses have been elucidated by analysis of induction of STAT target genes, and of mice rendered deficient in Jak and STAT genes. Cytokine signaling is modulated by crosstalk between the Jak-STAT pathway and pathways triggered by other major immune receptors, such as antigen receptors and receptors for inflammatory cytokines. Tight regulation of cytokine signaling is required for homeostasis, and several constitutive and inducible mechanisms for downregulation of Jak-STAT signaling have been described.