Behavioral sensitization to repeated natural homeostatic challenges, such as sodium deficiency and chronic stress and to artificial stimulants, such as amphetamines is well documented and characterized by increased and enduring responsiveness to the stimuli. Sodium deficiency enhances salt intake and sensitizes rats to the psychomotor effects of amphetamines and vice versa. Stress also contributes to amphetamine sensitization. This cross-sensitization between sodium deficiency and amphetamines and stress and amphetamines suggests that a common neural pathway is affected by all treatments. The mesolimbic dopamine system is one pathway that has been implicated in motivation and reward responses and changes in this system have been observed in sodium deficient, chronically stressed, and amphetamine treated rats. In the prenatal and/or early postnatal period chronic stress induces sensitization to amphetamines in offspring. Recent work in our laboratory suggests that early life dietary sodium manipulation, both sodium restriction and sodium excess, can cross-sensitize offspring to amphetamines. Low salt diets represent sodium deficiency, while high salt diets produce enhanced salt appetite in offspring. The underlying factor common to both diets may be increased stress associated with the diet which leads to amphetamine sensitivity. Understanding factors that contribute to individual differences in amphetamine sensitivity is of considerable importance. The possibility that alterations in prenatal and early postnatal sodium intake affect drug susceptibility in individuals is a new finding and may aid in the knowledge and prevention of drug abuse.