In recent years, rats selectively bred for high (HiS) or low (LoS) saccharin intake have provided valuable information regarding vulnerability to drug and food dependence, related affective disorders, and impulsive behavior. The HiS and LoS rats are models of the heritability of maladaptive behaviors, including hallmarks of drug dependence, bingeing, and withdrawal, which 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 will be presented regarding the importance of reactivity to aversive events in predicting drug abuse in HiS and LoS rats and other addiction-prone and -resistant phenotypes. Recent data from animal models also suggest that the addiction-prone and -resistant groups (e.g., HiS, LoS) respond in opposite ways when treated for drug abuse. Thus, assessing the severity of vulnerability may be an important consideration in designing treatment strategies for drug abuse in humans. This review focuses mainly on the behavioral overlap between drug abuse and excessive behavior directed toward natural rewards. The neurobiological bases for this interaction between drug and nondrug rewards have also been reviewed by others.