Regulations based on the precautionary principle should undertake a comprehensive assessment of all available scientific and technical data to identify sources of epistemic uncertainty. In the European Union (EU), environmental regulation is required to fulfill the principles established in Article 174 of the EU Treaty, such that it offers a high level of protection and is consistent with the precautionary principle. Pesticides in drinking water are currently regulated by the Drinking Water Directive using a maximum allowable concentration of 0.1 μg/L. This standard (a surrogate zero) was consistent with the precautionary principle when it was originally set in 1980 and remained consistent when retained in 1998. However, given developments in EU pesticide and water policy, international experience in regulating pesticides, and an increasing knowledge of pesticide toxicity, it can be argued that the level of epistemic uncertainty faced by regulators has substantially decreased. In this paper, we examine the extent to which such developments now challenge the basis of European drinking water standards for pesticides and whether, for substances for which there is good toxicological understanding, a regulatory approach based upon the World Health Organization (WHO) Guideline Value (GV) methodology would be more consistent with the principles underpinning European environmental policy.