OBJECTIVES: This study explores current applications (and potential future use) of the Efficiency Frontier (EF) in health economic evaluation. METHODS: We performed desk research on pharmacoeconomic guidelines for current usage of the EF and investigated possibilities for future use. RESULTS: Currently, the EF is officially used in 3 European countries. In Germany, since the enforcement of the ‘Act on the Reform of the Market for Medicinal Products’ (AMNOG) in January 2011, IQWiG applies the EF to determine non-arbitrary flexible thresholds across disease areas to ultimately determine an appropriate reimbursement price of new drugs (including interquartile-range to display uncertainty) in negotiations on request of the decision maker or manufacturer. In Belgium, the updated KCE guidelines dated July 2012 request the EF to identify the appropriate comparator among all relevant alternatives. In France, the updated HAS guidelines dated October 2012 require health interventions to be plotted on the EF to inform decision-making. In the future, the EF-approach could also be used to check on prices of national reference pricing clusters. Furthermore, the EF could help with priority setting (as suggested by the World Health Organization guide to cost-effectiveness analysis in 2003) and guiding or informing potential future (dis)investment decisions. The EF may also be combined with other approaches (e.g. making reimbursement decisions up to an ex ante fixed cost/outcome-threshold but setting prices beyond that level with the flexible EF). Lastly, it should not be overlooked that the EF can be applied for multiple purposes simultaneously. CONCLUSIONS: Since its first use to measure hospital efficiency, the EF is a valuable tool in health economics. Currently, its use diffuses within health economic evaluation and reimbursement decision-making. Yet, the full potential of the approach has not been exploited so far and the EF-approach remains under-researched by the scientific community.