Globally, the use of electronic cigarettes (e-cigs) has skyrocketed in the past several years. The impacts of e-cigs on the health of both humans and animals must be clarified. Thus, this chapter aims to provide a brief summary of findings from in vitro, in vivo, and clinical research that has drawn attention to the possible genotoxic and cytotoxic effects of e-cig vapor. The mechanism of action of e-cig vapor exposure is unclear, although its adverse effect on health involves the generation of trace metals and oxygen radicals and increased inflammation due to the propylene glycol (PG) and vegetable glycerine (VG) contents of e-liquid, both of which have the potential to be cytotoxic and genotoxic. Few studies on the possible consequences of e-cig usage that combine clinical, in vivo, and in vitro methods for long-term inhalation toxicity evaluations are available; hence, this chapter is imperative. The findings from this research revealed the harmful effects of e-cig aerosols on human health while also suggesting potential benefits. Exposure to e-cig vapor in a human model has been shown to alter pulmonary and vascular functions, interfere with lung homeostasis, increase the risk of myocardial infarction, and exacerbate inflammation and oxidative stress. Finally, e-cig use alters gene expression and molecular pathway regulation. According to the data acquired, e-liquid exposure may be hazardous to cells in vitro and to people and animals in vivo.