Current state practice still lacks a uniform approach to vaping regulation. The discrepancies are, at least in part, due to the uncertainties about the potential risks to human health resulting from vaping. In this context, the most plausible criteria justifying a given regulation are often rooted in the precautionary principle, which concentrates on “potential risks.” However, in the case of vaping regulation the assessment of potential risks has not been considered from the standpoint of a comparison with the well-known risks deriving from the consumption of traditional cigarettes. The EU Tobacco Products Directive, which provides for the harmonization of rules regarding e-cigarettes, is a good example of such an approach. In this chapter the authors, following a brief analysis of the features of the precautionary principle in the international and EU legal systems, investigate some of the distortions that appear when the precautionary principle is applied to vaping regulations.