Recent gains in the fight against malaria are threatened by the emergence and spread of artemisinin and partner drug resistance in Plasmodium falciparum in the Greater Mekong Subregion (GMS). When artemisinins are combined with a single partner drug, all recommended artemisinin-based combination therapies have shown reduced efficacy in some countries in the GMS at some point. Novel drugs are not available for the near future. Triple artemisinin-based combination therapies, combining artemisinins with two currently available partner drugs, will provide one of the last remaining safe and effective treatments for falciparum malaria that can be deployed rapidly in the GMS, whereas their deployment beyond the GMS could delay or prevent the global emergence and spread of resistance to currently available drugs. Artemisinin and partner drug resistance have resulted in high failure rates of artemisinin-based combination therapies (ACTs) in the GMS. Spread or emergence of resistance beyond the GMS are threats to malaria control.Triple ACTs (TACTs), combining an artemisinin and two existing partner drugs, could be a stop-gap therapy for treating multidrug-resistant malaria until new antimalarials are available. Where resistance is not established, deployment of TACTs could delay or prevent emergence of resistance and could prolong the longevity of antimalarial compounds used in any triple-drug combination.TACTs must be safe, well-tolerated, effective, and affordable. Fixed-dose combinations of three drugs in the same tablet will likely improve adherence. Barriers that hinder deployment and adherence must be identified and addressed early in the development of TACTs.