Nowadays, pharmaceuticals are present in surface waters as well as in groundwaters of developed countries. In the middle of Lake Geneva, for example, one of the largest European lakes, 14 pharmaceuticals are regularly detected in concentrations up to 0.37 µg/L. This pollution is due to the human consumption of drugs and also veterinary use and industrial releases during production. In the case of Lake Geneva, this latter pollution is significant for some specific compounds. But, as shown in this overview, environmental toxicity data are lacking for most of the pharmaceuticals detected in the aquatic environment. For example, the ecotoxicity of metformin, one of the main compounds detected in Lake Geneva, is mostly unknown for the moment. Furthermore, specific effects like endocrine disruption, genotoxicity, or antibioresistance induction, which may be expected because of the mode of action of some drugs, have not yet been investigated for aquatic species. Ecological risk assessment of pharmaceuticals is therefore tricky and most of the time is not feasible. Owing to this lack of knowledge, also due to high biological potency of the pharmaceuticals, it is critical to reduce the release of these compounds to the aquatic system. This may be achieved by ‘at source’ (e.g., urine collection) methods or ‘end of pipe’ (e.g., wastewater treatment) solutions. WIREs Water 2014, 1:69–86. doi: 10.1002/wat2.1006 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.