The availability of tobacco products purported to reduce toxin exposure or potentially reduce health risks necessitates the development of methods and identification of biomarkers that can be used to assess these products. These assessments occur on multiple levels and stages, from identifying constituents in the tobacco products and smoke, to human exposure and health effects trials, to postmarketing surveillance. A conference of multidisciplinary experts was convened to present and discuss methods and biomarkers to assess these products and to consider the infrastructure necessary to facilitate the evaluation process. Although no currently available set of measures was thought to be sufficient for determining the relative health risk of potential reduced exposure products, this paper provides a blueprint for future research toward this end.