Abstract The popularity of e-cigarettes has skyrocketed in recent years, and most vapers use flavored e-cigarette products. Consumption of flavored e-cigarettes exceeds that of combustible cigarettes and other tobacco products among adolescents, who are particularly vulnerable to becoming nicotine dependent. Flavorings have been used by the tobacco industry since the 17th century, but the use of flavors by the e-cigarette industry to create products with flavors (i.e. flavors other than tobacco or menthol) has sparked a public health debate. This review addresses the possibility that characterizing flavors make nicotine more appealing, rewarding and addictive. It also discusses ways in which preclinical and clinical studies could improve our understanding of the mechanisms by which flavors may alter nicotine reward and reinforcement. This article is part of the special issue on ‘Contemporary Advances in Nicotine Neuropharmacology’.