E-cigarette use has been increasing globally over the past decade. Many use e-cigarettes as an alternative or method to quit cigarette smoking, whereas others use these products recreationally. As technology has advanced, many individuals have reported symptoms of dependence on these products and continue to use them beyond achieving abstinence from smoking. Despite individuals reporting interest in quitting, little is known about e-cigarette cessation. This systematic review sought to identify and evaluate all human subjects literature published on the outcome of e-cigarette cessation through September 2021. Of the 79 articles identified, 56 were cross-sectional, 6 were qualitative, 5 were cohort studies, 3 were experimental, 2 were mixed methods, and 7 reported intervention or case studies of e-cigarette cessation. Results showed youth generally had high intent to quit e-cigarettes, whereas results were mixed with adult samples. Youth were motivated to quit e-cigarettes by health concerns, whereas adults were motivated to quit e-cigarettes by cost, lack of satisfaction, and psychologic factors. Adults were more likely to report past e-cigarette quit attempts, most commonly “cold turkey.” Few interventions tested strategies for e-cigarette cessation, with a majority targeted for youth. Given the lack of information on e-cigarette cessation, recommendations for future studies are outlined.