Possible pathophysiological, clinical and epidemiological interactions between HIV and tropical pathogens, especially malaria are a concern in tropical areas. Two decades of research learned that HIV related immune suppression is correlated with increased malaria infection, burden and treatment failure and with complicated malaria irrespective of the immune status. The recent role out of antiretroviral therapies and new antimalarials as artemisinin combination therapies raise additional concerns regarding possible synergistic, antagonistic effects on efficacy and toxicity. Cotrimoxazole, used to prevent opportunistic infections, has shown to have strong antimalarial prophylactic properties despite its long term use and rising antifolate resistance. Administering efavirenz, an non-nucleoside reverse transcriptase inhibitor, with amodiaquine-artesunate has been has associated with increased toxicity. Recent in vivo observations confirmed that protease inhibitors have strong antimalarial properties. Ritonavir boosted lopinavir and artemether-lumefantrine had a synergistic effect in terms of improved malaria treatment outcomes with no apparent increase in risk of toxicity. Overall, for the prevention and treatment of malaria in HIV infected populations current standard of care is similar as in non-HIV infected. Available data show that the wider implementation of insecticide treated bednets, cotrimoxazole prophylaxis, and antiretroviral therapy might substantially reduce the morbidity of malaria in HIV-infected patients. With these observations, those accessing care for HIV infection are now, paradoxically, well protected from malaria. These findings therefore highlight the need for confirmatory diagnosis of malaria in HIV infected individuals receiving these interventions and provision of different artemisinin-based combination therapies to treat malaria therapy only when the diagnosis is confirmed. This article is protected by copyright. All rights reserved.