Research into the molecular biology of infectious diseases is mostly associated with well-developed countries. But in the midst of tropical Papua New Guinea, highly sophisticated molecular research has being conducted over years to understand and fight malaria and other tropical diseases. Here, we review such research carried out at the Papua New Guinea Institute of Medical Research. This Institute has considerably shaped research on molecular epidemiology through its analysis of the diversity and structure of the Plasmodium falciparum population. In addition, research has been conducted on human host factors and, more recently, the molecular analysis of drug resistance and the underlying molecular mechanisms of host-parasite interactions have been investigated.