Mass use of antimalarial drugs is likely to be required to eliminate the last parasites from a population. Drugs that have been used in millions of individuals to eliminate infectious diseases include azithromycin (trachoma), ivermectin / albendazole (filaria), and primaquine (malaria). Old drugs such as primaquine and methylene blue are currently available to stop transmission while the only new product likely to become available soon is a long acting primaquine analogue, tafenoquine. When giving medications to entire populations it is vital that the drugs be extremely safe and inexpensive. Both primaquine and tafenoquine carry a G6PD liability that could result in hemolysis in those with severely deficient erythrocyte enzyme activity. Primaquine has been successfully used in public health programs in the former Soviet Union and China to eliminate relapsing malaria. Estimated severe adverse event rates are 1:10,000 without G6PD screening. During the Vietnam War, 2.7 million US military members received 45mg primaquine weekly with an estimated SAE rate of 1:3000 without any deaths. Despite G6PD concerns it seems likely that a public health indication for tafenoquine can be devised that would be of particular use in malaria elimination in Asia where the predominant parasite continues to be Plasmodium vivax.