The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases.