JAKs (Janus Kinase; EC 2.7.10.2; 4 types identified) and STATs (Signal Transducer and Activator of Transcription; 7 types identified) are critical components of many cytokine receptor systems, regulating growth, survival, differentiation and pathogen resistance. (Cytokine) receptor-bound STATs phosphorylated by JAKs dimerize and translocate into the nucleus to regulate target gene transcription. In most cases, a specific JAK-STAT combination has been paired with a specific member of the cytokine receptor family, and this information translated into cell-type specific patterns of cytokine responsiveness and gene expression. Members of the suppressor of cytokine signaling (SOCS) protein family dampen receptor signaling via homologous or heterologous feedback regulation. Consequently, Janus kinase mutations are major molecular events in human hematological malignancies.