In recent years, a huge and still growing number of electronic nicotine delivery systems (ENDS, or electronic cigarettes) has been introduced to the market. Despite the claims of the producer companies and the consumers' perception, ENDS safety is hotly debated, especially in comparison with combustible tobacco products. In this review, we focus on oxidative stress and alterations in antioxidant activity caused by ENDS' aerosols or liquids in oral cavity and lung tissues, which are the primary targets of cigarette smoke. Although detectable levels of oxidative stress are induced by ENDS, it should be emphasized that lower levels of oxidative stress markers and of related gene and protein alterations are observed compared to conventional cigarettes. More scientific studies need to be performed related to ENDS’ toxicity and induction of oxidative stress in a pathophysiological context in order to allow evidence based conclusions. Display omitted •Electronic nicotine delivery systems induce oxidative stress.•Electronic cigarettes induce lower oxidative stress compared to tobacco cigarettes.•Heat not burn tobacco products may be less harmful compared to traditional tobacco.•Potential additional harm caused by ENDs needs further investigation.