The growing rates of obesity have prompted comparisons between the uncontrolled intake of food and drugs; however, an evaluation of the equivalence of food- and drug-related behaviors requires a thorough understanding of the underlying neural circuits driving each behavior. Although it has been attractive to borrow neurobiological concepts from addiction to explore compulsive food seeking, a more integrated model is needed to understand how food and drugs differ in their ability to drive behavior. In this review, we will examine the commonalities and differences in the systems-level and behavioral responses to food and drugs of abuse, with the goal of identifying areas of research that would address gaps in our current understanding and ultimately identify novel treatments for obesity or drug addiction.