BACKGROUND:  Recent recommendations from the EU commission have given countries the responsibility to develop national strategies for rare diseases, including plans for inventorying of rare diseases and development of centers of excellence (CoE). In France, patients are required to consult or obtain their prescription from a CoE in order for reimbursement of orphan drugs to be granted. As CoE and rare disease registries are developed throughout the EU member states, increased awareness, education, and data collection will lead to better management of orphan diseases, monitoring of long-term outcomes and cost and opportunities for payer management. OBJECTIVE: To better understand the current and evolving roles of CoE and national disease registries in the EU, including implications on the price and management of orphan drugs, and to identify implications for further evolution of rare disease specialty centers in the US. APPROACH: Trends on the EU development of CoE and national rare disease registries will be reviewed and expert opinion will be consulted.  RESULTS: Tools and data that will be available to both the payer bodies and the CoE will be identified Examples of influence of CoE and disease registries on the pricing and reimbursement of orphan drugs (e.g.  CoE in France, cancer registries in Italy) will be described. Implications of the use of this information and data will be explored for EU payers.  CONCLUSIONS: EU payer bodies will gain increasing information and data necessary to further scrutinize the price and reimbursement opportunity for orphan drugs, through the use of registries and evaluation by CoE. Manufacturers should be prepared to understand and consider partnerships with CoE in EU.