Although comparative effectiveness has received considerable attention recently – especially in the USA – it is not a new concept. In Europe, it has been applied for some time now in the pricing and reimbursement processes of many countries. Each one uses it in its own way, however, with variations in the precise definition and the role it plays in the process. It remains to be seen whether the implementation of comparative effectiveness becomes more harmonized and whether it will be integrated better with the registration process. Regardless of the extent to which it is standardized, obtaining the data will remain a substantial hurdle, both methodologically and operationally. Everyone wants comparative effectiveness information but no one knows quite how to make it happen.