JAK-STAT pathway has been implicated in the pathogenesis of metabolic disorders including diabetes and obesity. Diabetes mellitus characterized by chronic hyperglycemia is a group of metabolic diseases. Polymorphism studies in humans (JAK2 gene) and knockout studies (JAK3 gene) in mice have implicated JAK-STAT pathway in the pathogenesis of diabetes. Obesity that is defined by an accumulation of excessive fat is a complex disorder that can increase risk of diseases and health problems. Mice deficient in Tyk2 are prone to obesity; in contrast, deletion of Stat4 leads to attenuated adipose tissue inflammation. In this chapter, I discuss various facets of diabetes and obesity, and role of JAK-STAT molecules in adipose tissues. The link between central nervous system and obesity and role of JAK-STAT signaling towards food intake are also discussed. I finish the chapter by mentioning the potential therapeutics targeting the JAK-STAT pathway to fight diabetes and obesity.