Electronic Nicotine Delivery Systems (ENDS) have divided the tobacco control community. Although some e-liquids and the aerosols produced by e-cigarettes have been found to contain a number of potentially harmful toxins, they are at substantially lower levels than those present in tobacco, and humans’ actual exposure is at levels similar to medically licensed nicotine replacement therapies. As a result, Public Health England has declared ENDS to be around 95 percent less harmful than combustible cigarettes. Moreover, while the evidence is currently too weak to draw firm conclusions regarding ENDS’ impact on smoking cessation, findings from population studies and a handful of clinical trials indicate there appears to be a benefit in this regard. This chapter summarizes and critically assesses the current scientific knowledge on the use of ENDS, particularly with regard to their safety and efficacy as a cessation or harm reduction device.