Electronic cigarettes (e-cigarettes) have attracted much attention as a new substitute for conventional cigarettes. E-cigarettes are first exposed to the respiratory system after inhalation, and studies on the toxicity mechanisms of e-cigarettes have been reported. Current research shows that e-cigarette exposure may have potentially harmful effects on cells, animals, and humans, while the safety evaluation of the long-term effects of e-cigarette use is still unknown. Similar but not identical to conventional cigarettes, the toxicity mechanisms of e-cigarettes are mainly manifested in oxidative stress, inflammatory responses, and DNA damage. This review will summarize the toxicity mechanisms and signal pathways of conventional cigarettes and e-cigarettes concerning the respiratory system, which could give researchers a better understanding and direction on the effects of e-cigarettes on our health.