In 2004 a large focus of Plasmodium knowlesi malaria was reported in the human population in Sarawak, Malaysian Borneo. Plasmodium knowlesi, a parasite of the South-East Asian macaques (Macaca fascicularis and Macaca nemestrina), had entered the human population. Plasmodium knowlesi is transmitted by the leucosphyrus group of Anopheline mosquitoes and transmission is largely zoonotic and restricted to the jungle setting. Humans entering jungle transmission sites are at risk. Since 2004, human cases of P. knowlesi have been continuously reported in local communities and in travellers returning from South East Asia. Plasmodium knowlesi is the most common type of indigenous malaria reported in Malaysia. Infections are most often uncomplicated but at least 10% of patients report with severe malaria and 1–2% of cases have a fatal outcome. Parasitaemia is positively associated with the clinical and laboratory markers of severe malaria. The current literature on P. knowlesi, including epidemiology, natural hosts and vectors, pathogenesis, clinical descriptions, treatment and diagnosis, is reviewed. There are many gaps in our understanding of this disease that are highlighted here with suggestions for further research to inform pre-emptive