Cost-effectiveness analysis (CEA) is an analytic tool that provides a framework for comparing the health benefits and resource expenditures associated with competing medical and public health interventions, thereby allowing decision makers to identify interventions that yield the greatest amount of health, given their resource constraints. Models are important components of most, if not all, CEAs, and they play a key role in evaluating the cost-effectiveness of cancer screening programs, in particular. In this article, we describe the basic types of models used to evaluate cancer screening programs and provide examples of the use of models in CEAs and to guide cancer screening policy. Finally, we offer some suggestions for important concepts to consider when interpreting model results.