Tens of thousands of man-made chemicals are in everyday use in developed countries. A high proportion of these, or their transformation products, probably reach the aquatic environment. A considerable amount is known about the environmental concentrations of some of these chemicals (such as metals), especially the regulated ones, but little or nothing is known about the majority. In densely populated countries, most or all rivers will receive both diffuse (e.g. agricultural runoff) and point source (e.g. sewage treatment plant effluent) inputs, and hence be contaminated with complex, ill-defined mixtures of chemicals. Most freshwater organisms will be exposed, to varying degrees, to this contamination. The number of species exposed is in the thousands, and quite possibly tens of thousands. Little is known about whether or not these species are adversely affected by the chemicals present in their environment. Often it is not even known what species are present, let alone whether they are affected by the chemicals present. In a few high-profile cases (e.g. tributyl tin causing imposex in molluscs and oestrogens ‘feminizing’ male fish), chemicals have undoubtedly adversely affected aquatic species, occasionally leading to population crashes. Whether or not other chemicals are affecting less visible species (such as most invertebrates) is largely unknown. It is possible that only very few chemicals in the freshwater environment are adversely affecting wildlife, but it is equally possible that some effects of chemicals are, as yet, undiscovered (and may remain so). Nor it is clear which chemicals may pose the greatest risk to aquatic organisms. All these uncertainties leave much to chance, yet designing a regulatory system that would better protect aquatic organisms from chemicals is difficult. A more flexible and intelligent strategy may improve the current situation. Finally, the risk due to chemicals is put into context with the many other threats, such as alien species and new diseases that undoubtedly can pose significant risks to aquatic ecosystems.