Human infections with the simian malaria parasite, Plasmodium knowlesi, were thought to be extremely rare, until a large focus of human infections were reported in the Kapit Division of Sarawak, Malaysian Borneo in 2004. Since then, human knowlesi malaria cases have been reported throughout Malaysian Borneo and in all countries in Southeast Asia. The actual incidence of knowlesi malaria is not known since molecular detection methods are necessary to differentiate it from the morphologically identical P. malariae, and these methods are not routinely utlised. In Malaysian Borneo, knowlesi malaria is the most common cause of malaria, accounting for all the indigenous cases in Sarawak and in some parts of Sabah, Malaysian Borneo. The primary natural hosts of P. knowlesi are long-tailed and pig-tailed macaques. P. knowlesi is an ancient malaria parasite which is transmitted by forest-dwelling vectors that prefer to feed outdoors. As long as there is a huge reservoir of P. knowlesi parasites among non-human primates, methods aimed at eradicating malaria such as early detection and treatment, provision of insecticide-treated bednets and spraying of dwellings with insecticides will not be effective against zoonotic knowlesi malaria.