This review is aimed at understanding some of the common neurochemical, behavioral and physiological determinants of drug and food overconsumption. Much current work has been devoted to determining the similarities between the brain circuits controlling excessive use of addictive drugs and the overconsumption of palatable foods. The brain systems involved likely include peptides of both mesolimbic and hypothalamic origin. Evidence gathered from expression and injection studies suggests that the consumption of drugs, such as ethanol and nicotine, and also of palatable foods rich in fat is stimulated by different orexigenic peptides, such as enkephalin, galanin, orexin, and melaninconcentrating hormone, acting within the hypothalamus or various limbic structures, while another peptide, neuropeptide Y, is closely related to carbohydrate consumption and shows an inverse relationship with ethanol and nicotine consumption. Moreover, studies in animal models suggest that a propensity to overconsume these reinforcing substances may result from preexisting disturbances in these same peptide systems. These neurochemical disturbances, in turn, may also be closely linked to specific behaviors associated with excessive consummatory behavior, such as hyperactivity or novelty-seeking, palatable food preference, and also fluctuations in circulating lipid levels. Clear understanding of the relationship between these various determinants of consummatory behavior will allow researchers to effectively predict and examine at early stages of exposure animals that are prone to drug and food overconsumption. This work may ultimately aid in the identification of inherent traits that increase the risk for drug abuse and palatable food overconsumption.