The unprecedented levels of political, technical and financial support for improved malaria control, and particularly for changes in the malaria treatment policy, have heralded a renewed appreciation of the role of pharmacovigilance, its relationship with other areas of public health and the development of novel approaches to addressing the pharmacovigilance priorities in malaria-endemic countries. In order to become a valuable public health activity in these resource-limited settings, pharmacovigilance needs to be viewed within its broadest definition of detecting, understanding and preventing adverse drug reactions and drug-related problems. Pharmacovigilance in resource-limited settings provides an opportunity to identify and address health system failures that significantly impact on patient morbidity and mortality, particularly those that are drug related. Countries need to establish a national strategy that identifies realistic and relevant objectives that meet the most pressing pharmacovigilance needs, taking into consideration the conditions under which these systems are likely to develop.