The most widely used approach to conduct in vivo drug efficacy trials in the Americas follows the guidelines of the WHO (WHO 2009) with the modifications recommended by the Pan American Health Organization for studies in the Americas (PAHO 2003). The goal of such studies is to assess antimalarial drugs currently being used for first-line treatment of uncomplicated malaria. Much of the effort to monitor antimalarial efficacy in the Americas has been done as part of the Amazon Network of Antimalarial Resistance Monitoring and the Amazon Malaria Initiative (PAHO 2012). This information is critical for guiding the development of rational antimalarial drug policies in endemic areas.