As access to inexpensive energy-dense foods increases and lifestyles become ever more sedentary obesity levels have climbed. The mesoaccumbens dopamine system is essential to maintaining appropriate control over feeding and associated behaviors. Emerging evidence suggests that consumption of highly palatable energy-dense food profoundly impacts mesoaccumbens dopamine neurotransmission and downstream signaling cascades in cortical and limbic regions. Furthermore, it is increasingly clear that dysregulation of dopamine receptor function contributes to the emergence of compulsive food intake, which likely contributes to weight gain, development of obesity and difficulties losing weight. Understanding the nature of these perturbations in mesoaccumbens dopamine may reveal novel strategies for medications development to combat obesity and obesity-associated diseases.