HIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim-sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistance-conferring mutations that are currently common in Africa. Nonetheless, additional interventions are needed to protect HIV-infected people that reside in high-malaria-transmission areas. Artemether-lumefantrine and dihydroartemisinin-piperaquine are highly efficacious and safe for the treatment of uncomplicated malaria in HIV-infected persons. Coadministration of antiretroviral and antimalarial drugs creates the potential for pharmacokinetic drug interactions that may increase (causing enhancement of malaria treatment efficacy and post-treatment prophylaxis and/or unanticipated toxicity) or reduce (creating risk for treatment failure) antimalarial drug exposure. Further studies are needed to elucidate potentially important pharmacokinetic interactions between commonly used antimalarials, antiretrovirals and TS and their clinical implications. Data on the benefits of long-term TS prophylaxis among HIV patients on antiretroviral therapy who have achieved immune-reconstitution are limited. Studies to address these questions are ongoing or planned, and the results should provide the evidence base required to guide the prevention and treatment of malaria in HIV-infected patients.