Overconsumption of high caloric food plays an important role in the etiology of obesity. Several factors drive such hedonic feeding. High caloric food is often palatable. In addition, when an individual is sated, stress and food-related cues can serve as potent feeding triggers. A better understanding of the neurobiological underpinnings of food palatability and environmentally triggered overconsumption would aid the development of new treatment strategies. In the current review we address the pivotal role of the mesolimbic dopamine reward system in the drive towards high caloric palatable food and its relation to stress- and cue-induced feeding. We also discuss how this system may be affected by both established and potential anti-obesity drug targets.