Biomarkers provide a dynamic and powerful approach to understanding the spectrum of neurological disease with applications in observational and analytic epidemiology, randomized clinical trials, screening and diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer the means for homogeneous classification of a disease and risk factors, and the can extend our base information about the underlying pathogenesis of disease. Biomarkers can also reflect the entire spectrum of disease from the earliest manifestations to the terminal stages. This brief review describes the major uses of biomarkers in clinical investigation. Careful assessment of the validity of biomarkers is required with respect to the stage of disease. Causes of variability in the measurement of biomarkers range from the individual to the laboratory. Issues that affect the analysis of biomarkers are discussed along with recommendations on how to deal with bias and confounding.