In this review, we relate both laboratory and clinical evidence associated with the capacity for estrogen to function as a modulator of nigrostriatal dopaminergic pathology. To accomplish this goal, we have divided this review into three parts. In Part 1, we provide a brief historical perspective of studies that have laid the groundwork for demonstrating the existence of hormonal- nigrostriatal interactions. In Part 2, we focus specifically on laboratory data that show the ability and conditions by which estrogen may function as a neuroprotectant of the nigrostriatal dopaminergic system. Finally, in Part 3, we review the clinical literature related to this issue as a means for consideration of estrogen as a modulator, neuroprotectant, and therapy for Parkinson disease.