Human nail clippings have been used in recent epidemiological studies as a routine bioindicator of arsenic and selenium exposure. To ensure sound application of this biomarker, however, it is important to consider properties and scientific knowledge pertaining to validation of this particular tool. In this review, the use of human nails to measure exposure to arsenic and selenium is discussed in the context of the biomarker validation framework. Literature related to both analytical procedures and intrinsic characteristics of the biomarker is reviewed. Specifically, the followings are addressed: sample collection and preparation methods, establishment of the exposure-biomarker relationship, intraindividual variability and reproducibility of measurements, and biomarker-disease investigations. Drawing from a rapidly growing body of literature, current knowledge of these biomarker validation steps is assessed. Therefore, this review brings attention to the important issue of biomarker validation, laying the framework for future studies measuring elemental composition of nails.