Methods and devices are provided for activating brown adipose tissue (BAT) with cooling. Generally, the methods and devices can activate BAT to increase thermogenesis, e.g., increase heat production in the patient, which over time can lead to weight loss and/or improved metabolic function. In one embodiment, a medical device is provided that activates BAT by cooling tissue having a high density of cold sensitive thermoreceptors and/or by cooling BAT depots directly, thereby increasing thermogenesis in the BAT and inducing weight loss and/or improved metabolic function through energy expenditure.