Objective: Anti-infectives are constantly discharged at trace levels in natural waters near urban centers and agricultural areas. They represent a cause for concern because of their potential contribution to the spread of anti-infective resistance in bacteria and other effects on aquatic biota. We compiled data on the occurrence of anti-infectives published in the last 24 years in environmental water matrices. The collected information was then compared with the available ecotoxicologic values to evaluate potential environmental concerns. Data sources: We used Web of Science and Google Scholar to search for articles published in peer-reviewed journals written in the English language since 1984. Data extraction: Information on compound concentrations in wastewaters and natural and drinking waters, the source of contamination, country of provenance of the samples, year of publication, limits of quantification, and method of analysis was extracted. Data synthesis: From the 126 different substances analyzed in environmental waters, 68 different parent compounds and 10 degradation products or metabolites have been quantified to date. Environmental concentrations vary from about 10−1 to 109 ng/L, depending on the compound, the matrix, and the source of contamination. Conclusions: Detrimental effects of anti-infectives on aquatic microbiota are possible with the constant exposure of sensitive species. Indirect impact on human health cannot be ruled out when considering the potential contribution of high anti-infective concentrations to the spreading of anti-infective resistance in bacteria.