In addition to the social, cultural and indirect medical complications of amphetamine analog abuse, this class of drugs is also known to have the potential to damage brain monoaminergic cells directly. Using methamphetamine as a prototype, this article provides a brief review of the history of amphetamine neurotoxicity research and the progress that has been made toward defining its characteristics. Remaining challenges for this line of investigation are outlined, and suggested avenues for addressing these challenges are provided.