Health systems administrators and clinicians need refined calculations of the attributable cost of infections due to drug-resistant microorganisms to develop and assess cost-effective prevention strategies that deal with these infections. To date, however, efforts to provide this information have yielded widely variable and often conflicting estimates. This lack of reproducibility is largely attributable to problems in study design and in the methods used to identify and measure costs. Addressing these methodological issues was the focus of a workshop that included participants from a broad range of backgrounds, including economics, epidemiology, health care management, health care outcomes research, and clinical care. This workshop summary presents the advantages and disadvantages of various research designs as well as particular methodological issues related to the measurement of the economic cost of resistance in health care settings. Suggestions are made for needed common definitions and approaches, study areas for future research are considered, and priority investigations are identified.