Recent scientific advances are providing an opportunity to revisit strategies for cervical cancer prevention. How to invest health resources wisely, such that public health benefits are maximized-and opportunity costs are minimized-is a critical question in the setting of enhanced cytologic screening methods, human papillomavirus DNA testing, and vaccine development. Developing sound clinical guidelines and public health policy will require careful consideration of the incremental benefits, harms, and costs associated with new interventions compared with existing interventions, at both an individual and a population level. In addition to an intervention's effectiveness, public health decision making requires the consideration of its feasibility, sustainability, and affordability. No clinical trial or single cohort study will be able to simultaneously consider all of these components. Cost-effectiveness analysis and disease-simulation modeling, capitalizing on data from multiple sources, can serve as a valuable tool to extend the time horizon of clinical trials, to evaluate more strategies than possible in a single clinical trial, and to assess the relative costs and benefits of alternative policies to reduce mortality from cervical cancer.