Degenerative diseases of the nervous system impose substantial medical and public health burdens on populations throughout the world. Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are three of the major neurodegenerative diseases. The prevalence and incidence of these diseases rise dramatically with age; thus the number of cases is expected to increase for the foreseeable future as life spans in many countries continue to increase. Causal contributions from genetic and environmental factors are, with some exceptions, poorly understood. Nonetheless, molecular epidemiology approaches have proven valuable for improving disease diagnoses, characterizing disease prognostic factors, identifying high-risk genes for familial neurodegenerative diseases, investigating common genetic variants that may predict susceptibility for the non-familial forms of these diseases, and for quantifying environmental exposures. Incorporation of molecular techniques, including genomics, proteomics, and measurements of environmental toxicant body burdens into epidemiologic research, offer considerable promise for enhancing progress on characterizing pathogenesis mechanisms and identifying specific risk factors, especially for the non-familial forms of these diseases. In this chapter, brief overviews are provided of the epidemiologic features of PD, AD, and ALS, as well as illustrative examples in which molecular epidemiologic approaches have advanced knowledge on underlying disease mechanisms and risk factors that might lead to improved medical management and ultimately disease prevention. The chapter concludes with some recommendations for future molecular epidemiology research.