This article reports on the 'Assessing Cost-Effectiveness' (ACE) initiative in priority setting from Australia. It commences with why priority setting is topical and notes that a wide variety of approaches are available. In assessing these various approaches, it is argued that a useful first step is to consider what constitutes an 'ideal' approach to priority setting. A checklist to guide priority setting is presented based on guidance from economic theory, ethics and social justice, lessons from empirical experience and the needs of decision-makers. The checklist is seen as an important contribution because it is the first time that criteria from such a broad range of considerations have been brought together to develop a framework for priority setting that endeavors to be both realistic and theoretically sound. The checklist will then be applied to a selection of existing approaches in order to illustrate their deficiencies and to provide the platform for explaining the unique features of the ACE approach. A case study (ACE-Cancer) will then be presented and assessed against the checklist, including reaction from stakeholders in the cancer field. The article concludes with an overview of the full body of ACE research completed to date, together with some reflections on the ACE experience.