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Human-use medicines are introduced into surface water throughout their entire life cycle, from manufacturing and consumption to improper disposal, resulting in negative effects on aquatic flora and fauna. Sustainability approaches have addressed this issue, proposing frameworks like the One Health approach. A revised definition of the rational use of medicines has also been proposed, taking into account their environmental sustainability. Building on this updated definition, this paper presents a decision-making flowchart to integrate the assessment of the impact of human medicines on surface water, outlining existing actions and proposing new ones. These actions are categorized into those with primary clinical benefits and those focused solely on environmental concerns. They include both upstream and downstream measures, such as implementing regulations similar to those in the EU and the USA, educating future healthcare practitioners, promoting green pharmacy innovations, and establishing proper disposal practices.