<p>The revision of the European Union (EU) Pharmaceutical Legislation aims for a competitive environment for innovation in the EU, including actions to support the development and approval of orphan medicines. In this article, we look at the Food and Drug Administration (FDA) for references to support this goal and discuss some FDA programs fostering innovation and competitiveness for orphan drugs in the US, including the Priority Review Voucher (PRV) program for Rare Paediatric Diseases, the Orphan Drug Grants to support clinical trials in orphan conditions and the recently launched Rare Disease Evidence Principles (RDEP) process. We further share some thoughts on how similar programs could be implemented in the EU, posing the European Medicines Agency (EMA) as a key figure to improve competitiveness for the development of orphan medicines in Europe.</p>