Insulin resistance is closely associated with obesity and type 2 diabetes. Although the mechanisms of insulin resistance are not fully elucidated, recent studies suggest that a complex interaction between inflammation, endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and autophagy dysregulation plays an important role in insulin resistance. The stress-activated c-Jun N-terminal kinase (JNK) has been increasingly recognized as a central mediator of insulin resistance. JNK mediates many of the effects of stress on insulin resistance through inhibitory phosphorylation of insulin receptor substrate, and suppression of the JNK pathway has been shown to improve insulin resistance and glucose tolerance. Therefore JNK may serve as a crucial link between stress and metabolic diseases as well as a promising therapeutic target. This review focuses on recent findings that support a critical role for JNK in the development of insulin resistance associated with inflammation, endoplasmic reticulum stress, oxidative stress and mitochondrial dysfunction. JNK regulation of autophagy and its implications in insulin resistance also will be discussed.