Malaria persists as an undiminished global problem, but the resources available to address it have increased. Many tools for understanding its biology and epidemiology are well developed, with a particular richness of comparative genome sequences. Targeted genetic manipulation is now effectively combined with in vitro culture assays on the most important human parasite, Plasmodium falciparum, and with in vivo analysis of rodent and monkey malaria parasites in their laboratory hosts. Studies of the epidemiology, prevention, and treatment of human malaria have already been influenced by the availability of molecular methods, and analyses of parasite polymorphisms have long had useful and highly informative applications. However, the molecular epidemiology of malaria is currently undergoing its most substantial revolution as a result of the genomic information and technologies that are available in well-resourced centers. It is a challenge for research agendas to face the real needs presented by a disease that largely exists in extremely resource-poor settings, but it is one that there appears to be an increased willingness to undertake. To this end, developments in the molecular epidemiology of malaria are reviewed here, emphasizing aspects that may be current and future priorities.