From David Livingstone’s Zambesi expedition onwards, South-Central Africa had been a crucial region in the history of modern antimalarial drugs. Quinine and other antimalarials (such as totaquine, mepacrine and paludrine), were at the heart of colonial health culture in the tropics. Arguably, more than any other drug, quinine defined the medical experience for many colonialists in Central Africa. At first an expensive medicine reserved for Europeans (who used it for myriad ailments), quinine gradually became available to some Africans, despite considerable fluctuations in its reputation and usage. During the world wars, antimalarials became increasingly an imperial concern. This paper explores the history of quinine and its alternatives as mobile medicines that connected medical practices in the Zambesi and Malawi regions with international pharmaceuticals, imperial politics and colonial knowledge-production. It highlights the debates and contests about the use of different antimalarials, and traces changes in their availability and use according to race, gender and class.