This report reviews the connections between environmental change, modern agricultural practices and the occurrence of infectious diseases - especially those of poverty; proposes a multi-criteria decision analysis approach to determining the key research priorities; and explores the benefits and limitations of a more systems-based approach to conceptualizing and investigating the problem. The report is the output of the Thematic Reference Group on Environment, Agriculture and Infectious Diseases of Poverty (TRG 4), part of an independent think tank of international experts, established and funded by the Special Programme for Research and Training in Tropical Diseases (TDR) to identify key research priorities through review of research evidence and input from stakeholder consultations. The report concludes that mitigating the outcomes on human health will require far-reaching strategies - spanning the environment, climate, agriculture, social-ecological, microbial and public-health sectors; as well as inter-disciplinary research and intersectoral action. People will also need to modify their way of thinking and engage beyond their own specialities, since the challenges are systemic and are amplified by the increasing inter-connectedness of human populations. This is one of a series of disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at www.who.int/tdr/capacity/global_report.