Environmental investigations of former industrial sites often detect the presence of chemicals for which no soil criteria exist and for which regulatory agencies have not derived estimates of toxic potency. This poses a considerable problem for making informed risk management decisions involving sites where such chemicals are present. As a result, a methodology has been developed for making risk-based decisions for chemicals of unknown toxic potency in soil at contaminated sites. The method is based on principles and procedures used by the US Food and Drug Administration (USFDA), the US Environmental Protection Agency (USEPA) and the Canadian Council of Ministers of the Environment (CCME). After analyzing the data on hundreds of carcinogenic and non-carcinogenic substances, the USFDA and other leading researchers have concluded that, if no toxicological data is available on a chemical, exposures less than 1.5 µg/person/day (i.e., 0.02 µg/kg body weight/day) are unlikely to result in appreciable health risks even if the substance was later found to be a carcinogen. To develop maximum soil concentrations that will be protective of human health (i.e., Risk Management Criteria or RMC), the above exposure limit of 0.02 µg/kg body weight/day has been assumed to be protective of risks from exposure to chemicals lacking toxicological data. Using a stochastic risk assessment model for estimating exposures to chemicals from contaminated sites, our analyses indicate that a soil concentration of 2 µg/g would be protective of human health for land uses that include residential, commercial, and industrial development provided no major indirect pathways exist at the site. If indirect pathways exists (e.g., vapor infiltration of soil gases, uptake of chemicals into garden produce, etc.), alternate RMC could be developed, that include such indirect pathways, using the methodology provided in this paper. Used by experienced risk assessors, the approach is a scientifically defensible screening method that will preclude many chemicals from unnecessary evaluation, while allowing risk assessors to focus efforts on chemicals of greater concern and make informed risk management decisions.