The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for transducing signals from a variety of metabolically relevant hormones and cytokines including growth hormone, leptin, erythropoietin, IL4, IL6 and IFNγ. A growing body of evidence suggests that this pathway is dysregulated in the context of obesity and metabolic disease. Recent development of animal models has been instrumental in identifying the role of JAK/STAT signaling in the peripheral metabolic organs including adipose, liver, muscle, pancreas, and the immune system. In this review we summarize current knowledge about the function of JAK/STAT proteins in the regulation of metabolism, and highlight new potential therapeutic targets for the treatment of obesity and diabetes.