Although malaria remains one of the most important infectious causes of morbidity and mortality world-wide with 40% of the global population at risk, significant progress has been made toward elimination, notably with the development and use of rapid diagnostic tests, insecticide-treated bed nets, indoor residual spraying, and artemisinin-based combination therapies (ACTs). P. falciparum infection remains the most common cause of severe infection and death, but non-P. P. falciparum infections, including the recently emerged 5th plasmodium species, P. knowlesi, are increasingly recognized as causes of severe disease, especially in Southeast Asia. Chemotherapy for severe infections has been revolutionized following results of the SEQUAMAT and AQUAMAT trials showing that parenteral artesunate (versus quinine) reduced severe malaria mortality by 34.7% and 22.5% in Asian adults and African children, respectively, making it the drug of choice for severe malaria. However, rising rates of artemisinin resistance, currently confined to the Greater Mekong sub-region, are threatening the long-term efficacy of artemisinins. HIV infection remains an important risk factor for death and severe disease due to malaria. The full amplitude of mutual interactions between these conditions is only beginning to be elucidated while the complex, multi-directional and pharmacokinetic interactions between antimalarial agents and HIV drugs continue to emerge.