Despite successes with reducing global malaria mortality, malaria control efforts with chemotherapy present ongoing technical and programmatic challenges. Resistance to artemisinin-combination therapy and other antimalarials presents a major challenge, particularly in South East Asia. The prospect of radical cure of Plasmodium vivax hypnozoites with tafenoquine and new dosing strategies for primaquine are encouraging, but full integration into malaria control programmes remains difficult. Outside treatment of symptomatic malaria of individuals, new knowledge about intermittent presumptive treatment approaches for infants and pregnant women together with modelling for mass drug administration will underpin malaria control efforts into the future.