Nowadays, more than 30,000 chemicals (including pharmaceuticals, biocides and pesticides) are estimated to be of relevance for the aquatic environment. Wastewater has to be treated to meet the required quality for its reuse. Many approaches for the assessment of water quality are used or are under development. It is now widely accepted that none of these approaches is suitable to assess all the (micro)biological and chemical contaminants. Many processes for water and wastewater treatment have been proposed and researched, and some of them are already applied in routine treatment. Unfortunately, these are not able to completely remove most of the contaminants. In contrast, most often, each of them removes only a minor percentage. Some processes may even result in the formation of transformation products of widely unknown fate and effects. This clearly demonstrates the serious limitations of such end-of-pipe approaches like effluent treatment. Therefore, in the future, more attention has to be paid on the prevention of the introduction of such contaminants into the water cycle, i.e., by measures that have to be taken at the beginning of the pipe. Approaches helpful in this direction are presented here.