It has been suggested that exposure to stimulants alters the dopamine system and thus enhances sensitivity to stimulants and possibly other drugs. Sensitization has been induced experimentally in animals, especially in rats, and has been shown to be long-lasting. In addition, cross-sensitization across different compounds has been demonstrated. The animal data have raised concern that exposure to methylphenidate in childhood may enhance the risk for later abuse of stimulants and other drugs. We review the evidence bearing on sensitization in children treated with stimulants and followed into adulthood. None of four clinic-based studies found an excess of drug abuse in children previously treated with stimulants. A school-based longitudinal study obtained a relationship between early stimulant treatment and later drug use, without controlling for dinical confounds. The single prospective-controlled study of children who received placebo or methylphenidate does not support the sensitization hypothesis.