Mefloquine is an antimalarial drug developed by the U.S. Army Antimalarial Drug Program in conjunction with the World Health Organization and Hoffmann-La Roche to address the problem of chloroquine-resistant falciparum malaria encountered during the Vietnam War. Despite the expenditure of millions of dollars over a 20-year period, it is unlikely that mefloquine will ever be used for U.S. soldiers deployed to South East Asia. Although mefloquine met the specifications set by its developers, its usefulness is now limited by the rapid evolution of drug resistance following its release to the civilian population. Drug development for particular military needs was compromised by a rapid biological response from the parasite and military concerns. In an era of shrinking military budgets, military drug development programs will by necessity be more resource constrained, thus yielding fewer new drugs per decade. In the short term, emphasis should be directed toward adapting available antimicrobial drugs for antimalarial purposes.