Cost-effectiveness analysis has much conceptual attractiveness in priority setting but is not used to its full potential to assist policy-makers on making choices in health in developed or in developing countries. We call for a shift away from present economic evaluation activities—that tend to produce ad hoc and incomparable economic evaluation studies and, therefore, add little to the compendium of knowledge of cost-effectiveness of health interventions in general—toward a more systematic approach. Research efforts in economic evaluation should build on the foundations of cost-effectiveness research of the past decades to arrive at an informative methodology useful for national policy-makers. This strategy means that governments should steer sectoral cost-effectiveness analysis to obtain systematic and comprehensive information on the economic attractiveness of a set of new and current interventions, using a standardized methodology and capturing interactions between interventions. Without redirecting the focus of economic evaluation research, choosing in health care bears the risk to remain penny-wise but pound-foolish.