Obesity remains a pervasive global health problem. While there are a number of nonsurgical and surgical options for treatment, the incidence of obesity continues to increase at an alarming rate. The inability to curtail the growing rise of the obesity epidemic may be related to a combination of increased food availability and palatability. Research into feeding behavior has yielded a number of insights into the homeostatic and reward mechanisms that govern feeding. However, there remains a gap between laboratory investigations of feeding physiology in animals and translation into meaningful treatment options for humans. In addition, laboratory investigation may not be able to recapitulate all aspects of human food consumption. In a landmark pilot study of deep brain stimulation (DBS) of the lateral hypothalamic area for obesity, we found that there was an increase in resting metabolic rate as well as a decreased urge to eat. In this review, the authors will review some of the work relating to feeding physiology and research surrounding two nodes involved in feeding homeostasis, nucleus accumbens (NAc) and hypothalamus, and use this to provide a framework for future investigations of DBS as a viable therapeutic modality for obesity.