Introduction: Malaria remains one of the most important infectious diseases, causing around 655,000 deaths annually, mostly among children in Sub-Saharan Africa. Plasmodium falciparum, the parasite responsible for the most severe form of malaria, has developed resistance against almost all drugs in clinical use. Development of new drugs, preferably acting by mechanisms distinct from those of established treatment, is thus urgently needed.
Areas covered: Non-artemisinin drug candidates currently in pre-registration clinical trials are reviewed covering published data available until December 2011.
Expert opinion: Although promising compounds are presently undergoing clinical evaluation, the lack of new treatments for severe malaria and the predominance of artemisinin-based combination therapy for uncomplicated malaria is concerning. Future research should be directed towards the discovery of new therapeutic principles.