Worldwide, cigarette smoking is the major cause of premature mortality and diseases that can be prevented. Given that people continue smoking despite associated health risks, delivering nicotine without combustion should be considered a valuable and much less harmful way to reduce the public health burden caused by smoking. E‑cigarettes could play such a role if they were proven to be less harmful than combustible cigarettes. Although the number of clinical trials and human studies assessing the safety of e‑cigarettes is limited, numerous in vitro and in vivo studies reported on the potential harmful effects of the aerosol generated from e‑cigarettes. This article reviews the results of major clinical trials and laboratory studies with regard to cancer as well as cardiovascular and respiratory risk associated with the use of e‑cigarettes. Additionally, it also discusses the potential application of e‑cigarettes as smoking cessation tools. Most studies have indicated so far that e‑cigarettes are less harmful, but this applies only to smokers who completely switched to e‑cigarettes. In the opinion of the authors, good-quality research is crucial to establish the tolerance, safety, efficacy, and harm reduction potential of new technologies. Considering a significant role that physicians and other health providers play in helping smokers, there is an urgent need for evidence‑based guidelines and recommendations for clinical practitioners on potential benefits and risks of e‑cigarette use.