Electronic cigarettes (ECIGs) are a class of products that use an electrically powered heating element to aerosolise a liquid for user inhalation. One subgroup of the class, ‘closed-system’ ECIGs, is sold ready-to-use and is constructed of component parts that cannot be modified readily and are filled with liquids that cannot be accessed easily. Another subgroup of the class, ‘open-system’ ECIGs, allows the user to modify virtually every component part and/or fill them with any liquid. Thus, although any given closed-system ECIG can be considered a single product, any given open-system ECIG must be considered to be a nearly infinite number of products, as the user controls the system’s electrical power, heating element characteristics and liquid constituents, which almost always include solvents like propylene glycol and vegetable glycerin, sweeteners and flavourants, and at least one psychoactive drug such as nicotine or tetrahydrocannabinol. This user control is important because every aspect of ECIGs listed above—device power, heating element, liquid constituents—can influence the rate of toxicant (drug and non-drug) delivery to the user and thus user health. In part, because ECIGs deliver dependence-producing, psychoactive drugs and also because of concerns and increasing evidence that the aerosols that they emit are harmful, a variety of countries have acted to protect public health by banning the product class entirely (eg, Brazil, India and Uruguay) or regulating ECIG sales, marketing or use (eg, Canada, European Union, England, New Zealand and Philippines). Note that in no country are ECIGs approved as a therapeutic product. The goal of this commentary is to suggest that the current level of heterogeneity seen in open-system ECIGs is incompatible with effective regulation. To achieve this goal, we consider three potential ECIG regulations—reducing the availability of flavoured ECIG liquids, limiting liquid nicotine content and constraining nicotine emissions—and demonstrate that, in the context of …