Resource constraints and widespread poverty among populations undermine disease prevention in low- and middle-income countries (LMICs) and ensure that these countries carry a disproportionate share of the global disease burden. Lack of access to efficacious medicines in LMICs further exacerbates this inequity. Addressing inequitable access to medicines and assuring their sustainable use is critical to the well-being of these populations. Whilst inadequate access to medicines in LMICs has drawn much attention, less is known about the sustainable use of available medicines, particularly to ensure their efficacy and mitigate harm to the population and the environment. Uganda has adopted various measures to ensure sustainable medicines use, including a national medicines policy, essential medicines list, medicines regulation framework, and promotion of domestic medicines production. Despite progress, challenges remain to achieving sustainable medicines use in the country, including fragmented access, inappropriate use, poor-quality, and inappropriate disposal. There is need to consolidate the globally embraced One Health approach (fostering collaboration between human, animal and environmental health sectors) to addressing these challenges as espoused in the country’s One Health strategic plan. Medicines supply chain management in public sector health facilities needs to be strengthened to minimize inventory shortages (stock-outs). A strategy for universal health insurance can minimize economic barriers to medicines access. Enhanced professional and medicines regulation in the private health market needs to be implemented. There are opportunities to build further capacity in Uganda, particularly infrastructure for regulation of its healthcare systems, policy and governance, workforce capacity building, and population action and engagement.