To address the persistent problems of foodborne and zoonotic disease, public health officials worldwide face difficult choices about how to best allocate limited resources and target interventions to reduce morbidity and mortality. Data-driven approaches to informing these decisions have been developed in a number of countries. Integrated comparative frameworks generally share three methodological components: estimating incidence of acute illnesses, chronic sequelae, and mortality; attributing pathogen-specific illnesses to foods; and calculating integrated measures of disease burden such as cost of illness, willingness to pay, and health-adjusted life years (HALYs). To discuss the similarities and differences in these approaches, to seek consensus on principles, and to improve international collaboration, the E.U. MED-VET-NET and the U.S.-based Food Safety Research Consortium organized an international conference convened in Berlin, Germany, on July 19-21, 2006. This article draws in part on the deliberations of the conference and discusses general principles, data needs, methodological issues and challenges, and future research needs pertinent to objective data-driven analyses and their potential use for priority setting of foodborne and zoonotic pathogens in public health policy.