Type 2 diabetes mellitus is characterized by skeletal muscle insulin resistance and mitochondrial dysfunction; therefore, mitochondria have been considered a target for intervention to overcome muscle lipotoxicity and thereby treat diabetes. Indeed, exercise training, known to enhance mitochondrial metabolism, is one of the best strategies to prevent and treat type 2 diabetes. However, preclinical data also suggests that mitochondria can be targeted by non-exercise means, such as drugs and nutritional compounds, and that boosting mitochondrial function is associated with metabolic beneficial effects. In humans, we have previously shown that the dietary polyphenol resveratrol has beneficial effects on skeletal muscle mitochondrial function and metabolic health in humans, and that mitochondrial function can also be enhanced by the NAD+analogue acipimox. More recently, brown adipose tissue (BAT) has been identified as another target tissue to improve metabolic health in humans. BAT contains specialized mitochondria that express UCP1 and which can dissipate energy as heat. In humans, BAT is activated by acute cold exposure, and the total amount and activity of BAT can be increased by cold acclimation. We have shown that type 2 diabetic patients have very low levels of BAT. Most interestingly, cold acclimation in type 2 diabetes patients resulted in a very marked improvement in insulin sensitivity, although BAT activity was only marginally affected. In this presentation, recent data will be presented on the role of mitochondrial function and brown fat in metabolic health in humans.