The surge in the popularity of e-cigarettes has instigated ongoing research on their safety despite being advertised as a safe alternative to conventional cigarettes. There is ubiquity of reports showing that e-cigarette smoking induces biological and toxic alterations that increase the risk of cancer. Many investigators have shown that e-cigarette exposure can lead to changes in cellular metabolic activity, cytotoxicity, DNA damage, and an increase in inflammatory biomarkers. The extent of harm varies with the type of e-cigarette used, duration of exposure to e-cigarette vapors, and patterns of smoking. The cellular damage has been attributed mostly to the cytotoxicity of several ingredients of the e-cigarette liquid and aerosol, including nicotine and other chemical compounds. This chapter provides a review of the literature on e-cigarette use and its link to oral cancer, lung cancer, and bladder cancer.