In 2007 Timor-Leste, a malaria endemic country, changed its Malaria Treatment Protocol for uncomplicated falciparum malaria from sulphadoxine-pyrimethamine to artemether-lumefantrine. The change in treatment policy was based on the rise in morbidity due to malaria and perception of increasing drug resistance. Despite a lack of nationally available evidence on drug resistance, the Ministry of Health decided to change the protocol. The policy process leading to this change was examined through a qualitative study on how the country developed its revised treatment protocol for malaria. This process involved many actors and was led by the Timor-Leste Ministry of Health and the WHO country office. This paper examines the challenges and opportunities identified during this period of treatment protocol change.