Pharmaceuticals have been reported in surface waters, prompting legitimate public concern, as pharmaceuticals are biologically active compounds used daily by the public. Currently there are ecotoxicological data available for <1%, thus, the European Union Commission’s Scientific committee on Toxicity, Ecotoxicity, and Environment (CSTEE) recommended use of (Q)SAR models and precaution to prioritize further risk assessment of ∼4500 compounds and their adjuvants. We ranked 2986 different pharmaceutical compounds in 51 classes relative to hazard toward algae, daphnids, and fish using the EPIWIN program. This ranking cannot be used to acquit a compound based on predicted relative ranking. Modifying additives were the most toxic classes. Cardiovascular, gastrointestinal, antiviral, anxiolytic sedatives hypnotics and antipsychotics, corticosteroid, and thyroid pharmaceuticals were the predicted most hazardous therapeutic classes. The overall relative order of susceptibility was estimated to be daphnids>fish>algae. Expert judgment is needed to assess specific hazards for classes like microbial resistance and antibiotics, sex hormones, and endocrine disruptors. As human health and the function of ecological systems are interconnected and subject to the precautionary principle, harmonization of evidence for correlation and causality of adverse effects seems sensible in an ethical and cost-effective context to facilitate substitution of hazardous compounds. Data available: http://www.uoguelph.ca/~hsander/.