Malaria continues to wreak havoc in the Peruvian Amazon. Lengthy research efforts have brought important lessons on its particular epidemiology: the heterogeneous levels of transmission, the large reservoir of both asymptomatic and submicroscopic infections, the co-transmission of Plasmodium vivax and Plasmodium falciparum in the same areas, and the limitations of current diagnostics. Based on these features, the national elimination program could greatly benefit from simplified standard treatment, with the use of artemisinin-based combination therapy and even shorter schemes of primaquine maintaing the total dosing. It is acknowledged that there is some uncertainty regarding the true prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PD) and genetic polymorphisms related to cytochrome P-450 isozyme 2D6 functioning. Once we have a better understanding, tafenoquine, whether or not in combination with a rapid G6PD enzyme test, may become a future pathway to eliminate the otherwise hidden reservoir of the P. vivax hypnozoite through one standard Plasmodium treatment.