Polypeptide growth factors and cytokines elicit their effects by activating specific cell‐sur‐ face receptors, thereby initiating signaling cascades that culminate in the induction of specific subsets of genes. Initially identified as the primary mediators of interferon‐dependent signaling, JAKs and STATs are now known to be utilized by many different extracellular signaling proteins. In this report we describe how JAK‐STAT pathways transduce signals initiated by both cytokines and growth factors, focusing on how specificity is achieved through STAT‐receptor interactions and on how receptor‐associated kinases function in STAT activation. We also summarize current information on interactions between signaling pathways, particularly STAT‐Ras cross‐talk and the relative importance of these two pathways in regulating the transcription of target genes.—Leaman, D. W., Leung, S., Li, K., Stark, G. R. Regulation of STAT‐dependent pathways by growth factors and cytokines. FASEB J. 10, 1578‐1588 (1996)