The United Nations Environment Programme (UNEP) is currently coordinating negotiations to develop a binding global agreement by late in the year 2000 to prohibit, restrict, or reduce the production, use, or release of certain persistent organic pollutants (POPs). POPs are a small subset of organic chemicals whose characteristics of persistence in the environment, accumulation in biological organisms, and toxicity make them priority pollutants and environmental risks to humans and ecosystems. Under the UNEP negotiation, representatives are developing criteria and procedures for the addition of substances, guided by the initial list of 12 substances or substance groups selected for global action. It is therefore timely to investigate the scientific foundation for POPs screening criteria that have been used in other international, regional, and national programs, focusing on the properties of persistence, bioaccumulation, toxicity, and long-range transport in a policy context. The theoretical, empirical, and multimedia modeling approaches used reveal that guidance for setting POPs screening criteria can be developed using a combination of science and policy input. These approaches suggest that criteria adopted under regional POPs agreements in North America and Europe are reasonable and tend to isolate a limited number of clearly hazardous POPs from the majority of organic chemicals, while not being so stringent that the ability to respond to as yet unidentified risks is seriously compromised.