In the Fall of 1985 EPA’s Office of Radiation Programs (ORP) initiated a project to develop a formal approach to dealing with uncertainties encountered when estimating and evaluating risks to human health and the environment. Based on a literature review of modeling uncertainty, interviews with ORP technical and management staff, and input from experts on uncertainty analysis, a comprehensive approach was developed. This approach recognizes by design the constraints on budget, time, manpower, expertise, and availability of information often encountered in ’’real world’’ modeling. It is based on the observation that in practice risk modeling is usually done to support a decision process. As such, the approach focuses on how to frame a given risk modeling problem, how to use that framing to select an appropriate mixture of uncertainty analyses techniques, and how to integrate the techniques into an uncertainty assessment that effectively communicates important information and insight to decision-makers. The approach is presented in this report. Practical guidance on characterizing and analyzing uncertainties about model form and quantities and on effectively communicating uncertainty analysis results is included. Examples from actual applications are presented.