Methamphetamine is a potent addictive stimulant drug that activates certain systems in the brain. It is a member of the amphetamine family, but the effects of methamphetamine are much more potent, longer lasting, and more harmful to the central nervous system. Repeated administration of methamphetamine induces behavioral sensitization, which is considered to be related to compulsive drug-seeking behavior. Although the mechanism responsible for methamphetamine-induced behavioral sensitization remains unclear, it is believed that the mesolimbic dopaminergic system in the central nervous system plays a critical role in the development of behavioral sensitization. Our previous studies indicate that the involvement of the mu-opioid receptor system underlies the development of methamphetamine-induced behavioral sensitization. Understanding the mechanisms of behavioral sensitization that are regulated by the mu-opioid receptor system would be helpful in developing therapeutic programs against methamphetamine addiction. This review briefly discusses the neural circuitry and cellular mechanisms that are known to play a central role in methamphetamine-induced behavioral sensitization and outlines the role of the mu-opioid receptor system in the development of methamphetamine-induced sensitization.