The vesicular monoamine transporter-2 (VMAT-2) facilitates the sequestration of catecholamines and serotonin into synaptic vesicles, and is therefore an essential regulator of monoaminergic neuronal function. VMAT-2 proteins may also play a role in neuroprotection, since these transporters have the capacity to sequester neurotoxins within vesicles. Recent studies have demonstrated that psychostimulants, particularly dopamine "releasers" and "reuptake inhibitors", differentially alter VMAT-2 function. As described in this review, these studies not only provide insight into the pharmacological actions of stimulants, but also mechanisms underlying neurodegenerative disorders, including Parkinson's disease.