Currently available medications for malaria chemoprophylaxis are efficacious but the problems of patient compliance, the advance of parasite drug resistance, and real or perceived serious adverse effects mean that new chemical compounds are needed. Primaquine, which has been widely used to treat relapsing malaria since the 1950s, has been shown to prevent malaria when taken daily. Tafenoquine is a new 8-aminoquinoline with a much longer half-life than primaquine. Field trials to date indicate that tafenoquine is efficacious and can be taken weekly or perhaps even less frequently. Both primaquine and tafenoquine require exact knowledge of a person's glucose 6-phosphate dehydrogenase status in order to prevent drug-induced haemolysis. Other potential malaria chemoprophylactic drugs such as third-generation antifol compounds and Mannich bases have reached advanced preclinical testing. Mefloquine has been seen to cause serious neuropsychiatric adverse effects on rare occasions. Recent public controversy regarding reputedly common serious adverse effects has made many Western travellers unwilling to take mefloquine. Special risk groups exposed to malaria, such as long-term travellers, children, pregnant women, aircrew and those requiring unimpeded psychomotor reactions, migrants returning to visit malarious countries of origin and febrile persons who have returned from malaria endemic areas, all require a nuanced approach to the use of drugs to prevent malaria. The carrying of therapeutic courses of antimalarial drugs to be taken only if febrile illness develops is indicated in very few travellers despite its appeal to some who fear adverse effects more than they fear potentially lethal malaria infection. Travellers with a significant exposure to malaria require a comprehensive plan for prevention that includes anti-mosquito measures but which is still primarily be based on the regular use of efficacious antimalarial medications.