An ideal pharmaceutical treatment is both safe and effective for patients. However, from a sustainability perspective, it also needs to be cost-effective, energy- and resource-efficient, and not have a negative impact on the environment. When striving towards environmentally sustainable healthcare, trade-offs between environmental sustainability and other aspects play a multi-faceted role in decision-making along the whole life cycle of a pharmaceutical, from design to end-of-life. When making environment-driven choices, stakeholders in this life cycle (e.g., procurers, prescribers) may not be aware of all consequences (environmental, social, or economic), which complicates decision-making processes. Information at hand may be ambiguous or unknown due to data gaps, complex and interdependent local, national and global healthcare systems, and unknown future developments. Thus, trade-offs may happen at temporal or spatial scales outside of the daily practice of stakeholders. This commentary aims to initiate a discussion on these trade-offs, the need for a holistic view, the use of multi-criteria decision-making tools, and clear environmental sustainability guidelines.