E-cigarette use represents a public health controversy in the US and globally. Despite the potential of e-cigarettes to support cigarette cessation, their use increases health risks and risk for addiction, particularly in young people. Various federal, state, and local laws have impacted tobacco retail in general and e-cigarettes in particular. In the US, 2019–2020 federal laws increased in the minimum legal sales age for tobacco to 21 and banned flavored cartridge-based e-cigarettes. Many states and localities were early adopters of Tobacco 21 and implemented more comprehensive flavor restrictions than the federal ban. Meanwhile, cannabis retail is increasingly being legalized in the US—while cannabis-based product regulation has notable gaps at the federal, state, and local levels. These regulatory complexities have impacted specialized retailers selling e-cigarettes, including “vape shops” that exclusively sell e-cigarettes, “smoke shops” that sell e-cigarettes and other tobacco (and potentially CBD/THC and other un- or under-regulated products), and online retail. This commentary outlines public health concerns related to: (1) youth access; (2) consumer exposure to a broader range of tobacco products and marketing in retail settings where they may seek products to aid in cigarette cessation (i.e., such broad product exposure could hinder cessation attempts); (3) consumer exposure to un-/under-regulated products (e.g., delta-8-THC, kratom); and (4) federal, state, and local regulations being undermined by consumer access to prohibited products online and via the mail. These concerns underscore the need for ongoing surveillance of how retailers and consumers respond to regulations.