Overall, this review focuses mainly on the behavioral overlap and interaction between drug abuse and excessive behavior directed toward natural rewards. In recent years, rats selectively bred for high (HiS) or low (LoS) saccharin intake and tested for all phases of drug addiction have provided valuable information regarding vulnerability to drug (Carroll et al., Behav Pharmacol 19:435–60, 2008) and food (Avena, Appetite 55:734–7, 2010; Yakovenko et al., Appetite 57:397–400, 2011) dependence/addiction, related affective disorders, and impulsive behavior. The neurobiological bases for this interaction between drug and food rewards have been reviewed by others (Deadwyler, Ann N Y Acad Sci 1187:140–7, 2010; Volkow and Wise, Nat Neurosci 8:555–60, 2005; Olsen, Neuropharmacology 61:1109–22, 2011). The HiS and LoS rats are models of the heritability of maladaptive behaviors, including hallmarks of drug dependence, bingeing, and withdrawal that serve equally well for the understanding of binge eating. The purpose of this chapter is to review recent developments in this area of research, emphasizing that several commonalities between food and drug addiction have been revealed, and to highlight similar connections between other individual differences and their relationships to sweet preference and drug abuse. Impulsivity will also be discussed as a major marker of addiction vulnerability that covaries with sweet preference, as well as other vulnerability factors, such as age (adolescents vs. adults) and sex. New evidence is presented regarding the importance of reactivity to aversive events in predicting drug abuse in HiS and LoS rats and on the importance of other addiction-prone and addiction-resistant phenotypes. Recent data from animal models also suggest that the addiction-prone and addiction-resistant groups (e.g., HiS, LoS) respond in opposite ways when treated for drug abuse. Finally, new evidence shows the importance of self-initiated and self-maintained treatments to reduce vulnerability to behavioral excesses and incubation of craving after termination of their use.