The application of cost-effectiveness analysis to health care has been the subject of previous reviews. We address the use of economic evaluation methods in public health, including case studies of population-level policies, e.g., environmental regulations, injury prevention, tobacco control, folic acid fortification, and blood product safety, and the public health promotion of clinical preventive services, e.g., newborn screening, cancer screening, and childhood immunizations. We review the methods used in cost-effectiveness analysis, the implications for cost-effectiveness findings, and the extent to which economic studies have influenced policy and program decisions. We discuss reasons for the relatively limited impact to date of economic evaluation in public health. Finally, we address the vexing question of how to decide which interventions are cost effective and worthy of funding. Policy makers have funded certain interventions with rather high cost-effectiveness ratios, notably nucleic acid testing for blood product safety. Cost-effectiveness estimates are a decision aid, not a decision rule.