Most countries face high demands on their health care systems and have limited resources with which to meet them. Priority setting seeks to address these problems by proposing rules to decide which groups of patients or disease areas should secure favoured access to limited health care resources. The economic approach towards priority setting, particularly in the form of cost-effectiveness analysis, is commonly advocated. However, despite many decades of refinement of the technical and methodological issues arising from the use of economic evaluation in priority setting, decision makers continue to diverge frequently from the principles of economic evaluation. Our approach in this paper is to highlight the potential contribution of models of political economy to understanding what constitutes rational behaviour when agents operate within political and institutional constraints. We argue that there may be potentially greater benefits to be gained from exploration and analysis of priority setting using models based on concepts such as median voter and competing interest groups, than from further efforts to refine the techniques of economic evaluation.