The present study reviews options for reducing harm from pharmaceuticals that are known to cause adverse impacts by their presence in the environment. It reviews recent global and European Union policy development, which could go further in recognizing and addressing the issue in a global context. It considers green chemistry, which can help clean up production processes but holds only long‐term promise for creating “green” alternatives. It explores the potential of health promotion and disease prevention, which can contribute significantly to a reduction of the disease burden and thus the need for medicines, both for infectious and for noncommunicable disease. Eco‐directed sustainable prescribing practices are reviewed, which have been adopted successfully to reduce the use of harmful pharmaceuticals. We note recent developments in medicines optimization and precision medicine, which hold promise for improving patient outcomes, saving costs, and reducing pharmaceutical use, through individually tailored prescribing whereby the patient codecides their therapy. Waste prevention through reuse or redistribution is beginning to find public support and “take‐back” waste disposal schemes set up via extended producer responsibility systems have achieved high returns. Finally, the paper summarizes preferred advanced wastewater technologies, including innovative low‐cost, low‐energy options. In summary, although end‐of‐pipe options have a role to play, particularly for highly concentrated wastewaters, solutions further up the medicinal chain and disease prevention interventions, informed by a broad view of health and health care, are needed to pursue a much greater potential reduction of pharmaceuticals in the environment than can be achieved by end‐of‐pipe solutions alone. Environ Toxicol Chem 2023;00:1–11. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.