Repeated administration of addictive drugs causes cellular and molecular changes believed to be the mechanism of pro-addictive behaviors. Neuroadaptations also take place with repeated administration of amphetamine, methylphenidate and atomoxetine, drugs for Attention Deficit Hyperactivity Disorders (ADHD), and it is speculated that these changes may serve as markers to demonstrate the dependence liability of these therapies. In this review, we enumerate the neuroadaptive changes in molecules associated with neuronal signaling and plasticity, as well as neuronal morphology wrought by repeated administration of ADHD medications. We provide the current perspective on the dependence liability of these therapies, and also suggest of some factors that need to be considered in future investigations, so that what is drawn from animal studies would be better consolidated with those known clinically.