Objective: This article provides an overview of this theme issue of the American Journal of Health Behavior dedicated to electronic nicotine delivery systems (ENDS), with a special focus on JUUL. Methods: The author summarizes key findings from included papers and offers an evaluative perspective on ENDS as tools for smoking cessation versus the prospect of their appeal to previous non-smokers. Results: Delineation of certain metrics (eg, defining who is a smoker) and clarification about an acceptable level of unintended consequences weighed against harm reduction confound conclusions about the public health role of ENDS/JUUL. Conclusion: Until agreement on key definitions and performance of well-controlled studies, a system that promotes ENDS/JUUL use among smokers but discourages their use by never-smokers is a regulatory challenge.