Some cases of Parkinson's disease (PD) can be attributed to genetic mutations, others to specific environmental factors; yet the cause of a great majority of cases is unknown. Physical and emotional traumas were once briefly considered as factors in the pathophysiology of this disorder. With increasing evidence that stress can indeed increase neuronal loss in some brain regions, this hypothesis deserves to be reexamined. Stress increases the extracellular availability of glucocorticoids (GCs), dopamine (DA), and glutamate in the striatum as well as other brain regions. These factors undoubtedly can serve to enhance the functions of the striatum. However, each also has the capacity to be neurotoxic. Moreover, they can act synergistically to promote neuronal loss. Thus, we propose that stress might, indeed, be a key factor in the loss of DA neurons that underlies PD.