Methylphenidate (MPH) is widely used for narcolepsy, a sleep disorder, and attention-deficit/hyperactivity disorder (AD/HD). Considering that MPH has stimulating and awakening actions, the mechanisms underlying the MPH effect on narcolepsy are easy to understand. On the other hand, the mechanisms underlying effects of MPH on AD/HD are largely unknown. While MPH induces hyperactivity in healthy humans, MPH reduces hyperactivity in AD/HD patients. The main target molecules of MPH are dopamine transporter and norepinephrine transporter. Interestingly, mice lacking dopamine transporter show AD/HD-like behaviors and MPH reactions like those in AD/HD patients. Analyses of mice lacking dopamine transporter may lead to a better understanding of the neuropsychological MPH effects.