Household medical waste is often improperly disposed of in several countries, despite the presence of a collection mechanism. This study attempts to identify the challenges of medical waste collection systems, focusing on the regulatory instruments and the stakeholders involved in this process in Brazil, Chile, and Colombia. A descriptive analysis was conducted to identify the differences between these countries. The results reveal that, in general, only 7 out of the 20 regulatory instruments for solid waste are applied in the household medical waste collection process, focusing on the direct stakeholders in the human medicines market, from manufacturers to consumers. The main challenges identified are incorporating veterinary medicines, defining roles for all stakeholders involved, such as healthcare providers and health teaching institutions, and expanding the use of regulatory instruments. These findings support the use of legislation to reduce the stakeholder contributions gap for the collection of household medical waste.