Using a pilot system we have categorised this review as: “Historical question – no update intended: monotherapy no longer recommended" (see published notes). Malaria is a parasitic disease spread by mosquitoes that kills thousands of people worldwide. Multiple-drug-resistant malaria is widespread, and in South-East Asia resistance is high against nearly all single therapy antimalarial drugs. Here, and in other areas with low malaria transmission, the combination of artesunate and mefloquine may provide an effective alternative. The review includes eight trials, mainly from South-East Asia, that compared artesunate plus mefloquine with mefloquine alone for treating uncomplicated malaria. Artesunate plus mefloquine performed better at destroying blood parasites and reducing fever. Adverse events were similar with both treatments.