Wealthy, industrialized countries of the developed world successfully underwent the "epidemiologic transition" from infectious diseases to degenerative diseases, but developing countries have not yet achieved that transition. This article reviews the current status of Omran's Theory of Epidemiologic Transition, comparing the burden of infectious diseases in the developed world versus the developing world. The advent of modern sanitation and hygiene practices, effective vaccines, and antibiotics have significantly diminished the burden in the developed world, but infectious diseases remain the most common cause of death worldwide. The persistence of this disease burden has been due to a failure to employee effective strategies and to unforeseen developments, such as the emergence of HIV and the re-emergence of malaria and tuberculosis driven by newly developed drug resistance. The challenge in accurately assessing infectious disease burden and developing effective interventions is reviewed along with the most common diseases and current intervention strategies.