Electronic nicotine delivery systems (ENDS) are less harmful than combustible cigarettes but lack demonstrated safety. They may help some smokers to quit, while enticing future generations to smoke. The US regulatory environment has restricted research on ENDS for tobacco cessation yet extended the time for open market sales. Calls for further research ought not to stall regulatory action.Electronic nicotine delivery systems (ENDS; e.g. ecigarettes) have gained world-wide attention. Gaps in the evidence on ENDS have contributed to varied opinions, many passionately at odds. The National Academies of Sciences' (NAS) review of more than 800 research papers on ENDS was congressionally mandated and sponsored by the US Food and Drug Administration (FDA) to summarize the state of the science and identify research needs [1]. The NAS report provides a useful summary for policymakers, practitioners and researchers internationally and sheds light on the nuances in the risk/benefit equation for ENDS.Of the nearly 50 conclusions in the NAS report, the strongest evidence (deemed as substantial or conclusive) is listed in Box 1. Are ENDS harm-reducing or harm-creating? The answer is probably both. That is, ENDS may be harm-reducing for smokers seeking to quit (i.e. when the comparator is combustible tobacco), while harm-creating for former or never smokers, particularly among youth, for whom ENDS use appears to increase the risk of future use of combustible tobacco.Being less harmful than combustible cigarettes, which contribute to the deaths of two in three long-term users [2,3], does not mean ENDS are safe. ENDS aerosol contains nicotine, which is addictive; ultrafine particles, that can be inhaled deeply into the lungs; flavorings such as diacetyl, a chemical linked to serious lung disease; volatile organic compounds; cancer-causing chemicals; and heavy metals such as nickel, tin and lead, although all at lower levels than in combusted tobacco smoke [4]. This list is limited by the chemicals assayed to date. Other toxicants, yet to be determined, may be created by repeated heating of the plastic and metal devices.The NAS findings were incorporated into a dynamic population model, and the conclusion was a net public health benefit with reduced loss of life when modeled out to 2050. These gains, however, were lost when extended