Combination therapy is a cornerstone of modern malaria treatment, particularly in the context of widespread multidrug resistance. Using two or more antimalarial drugs with different mechanisms simultaneously enhances efficacy, shortens treatment duration, improves compliance and delays the development of resistance. Artemisinin-based combination therapies (ACTs), such as artemether–lumefantrine, artesunate–amodiaquine and artesunate–sulfadoxine/pyrimethamine, are highly effective in rapidly clearing parasites and reducing gametocyte carriage. They are also generally well tolerated. Non-artemisinin combinations, quinine-based regimens and novel combinations (e.g. piperaquine–dihydroartemisinin) offer alternative therapeutic options, although clinical experience with these remains limited. Although ACTs are the preferred first-line treatment, factors such as cost, local drug resistance patterns, safety during pregnancy and paediatric use must inform implementation and policy decisions.