Studies of the relation between exposure to drinking water disinfection by-products and pregnancy outcomes have been limited by the complexity of the exposure itself (consisting of hundreds of different chemicals), the diverse pathways contributing to exposure, and the difficulty in assessing behavioral determinants of exposure. Therefore, exposure biomarkers offer great promise of enhancing exposure assessment, the limiting factor in the quality and conclusiveness of epidemiologic studies. However, there are significant conceptual and logistical challenges in developing biomarkers for the various constituents of concern that are sensitive to typical variation in exposure, reflective of the time periods of interest, not susceptible to interference from exposures other than water, not subject to reverse causality by correlates of adverse pregnancy outcomes, reflective of the chemicals of interest, and feasible for large-scale epidemiologic studies. Urinary trichloroacetic acid has been the leading candidate exposure biomarker for over a decade, and the first attempt to incorporate it into an epidemiologic study (Am J Epidemiol. 2012;175(4):263-275) is notable-the considerable limitations notwithstanding. In future efforts, investigators need to combine biomarker development with substantive epidemiologic studies to improve on this initial effort and prepare for more definitive research.