This article highlights the complex interactions between anthropogenic ecological change and mosquito-borne disease patterns. Ancient Rome provides a historical case study of the possible interplay between deforestation and an increasing malarial disease burden, and examples drawn from across the globe suggest that the experience of Rome is being repeated today. The evidence calls for careful management of agricultural clearing and for a multidisciplinary perspective in policy development on the issue, particularly in regions where there are already indications of escalating disease rates.