Objective: To review the effectiveness and feasibility of risk managementstrategies implemented for drugs with significant known risks.Data Sources: Published medical literature and regulatory archives, includingproceedings of Food and Drug Administration advisory committee meetings.Iterative searches of the medical literature, the Internet, and Web-basedgovernment information sources were conducted throughout 2002-2003.Search terms were related to risk management, drug safety, and the names ofspecific medications known to be subject to risk management programs.Study Selection: Key studies that illustrated examples of risk managementand evaluated risk management programs were selected by the authors.Data Extraction: Performed manually by the authors.Data Synthesis: Much of the information regarding the effectiveness ofrisk management interventions in reducing risk is anecdotal; little informationhas been published. Given the demand for evidence-based clinical decisionmaking, pharmaceutical manufacturers and the health care communitymust understand whether these programs are achieving their ultimate goalsof reducing risks to patients, while making needed therapies available. Thispaucity of evidence points to new opportunities for researchers across disciplinesto better understand the feasibility and effectiveness of these interventionsand the impact of the interventions at the patient, practitioner, and publichealth levels. Such research needs to be published so that future programsand policy can be informed by these early examples.Conclusion: For interventions to be effective in reducing risk, they musteffect change in physician prescribing, pharmacist dispensing, and patientadherence. Risk intervention programs that are overly burdensome to physicians,pharmacists, or patients are unlikely to succeed in achieving the desiredoutcome of reducing individual risk. In addition, risk management programsshould be scaleable and implemented in a systematic fashion to accommodatemultiple simultaneous programs that can effectively manage the risk, ratherthan through a piecemeal approach.Keywords: Risk management, drug safety, risk-benefit profile, medicationguides, patient registries, physician registries.