Economic analyses can provide valuable information for health care decision makers. Systematic reviews of economic analyses can integrate information from multiple studies and provide important insights by systematically examining how differences between models lead to different results. We use our experience in developing and implementing systematic reviews of economic analyses for the U.S. Preventive Services T ask Force, particularly our systematic review of the cost-effectiveness of colorectal cancer screening, to illustrate key methodologic challenges and suggest a framework for other researchers in this area.