Recently, it was concluded that the optimal therapy for essential thrombocythemia and polycythemia vera, either recombinant interferon alpha (rIFNα) or hydroxyurea can only be determined by the completion of a randomized clinical trial. We present our recommendations for the use of rIFNα for those patients who are not candidates for the randomized trial. We argue for rethinking the approach whether we should continue to wait for the results from a randomized trial before recommending treatment with rIFNα for those unable and unwilling to enter these trials. The interferon story shows that clinical experience may be an alternative path to follow when making treatment decisions and recommendations in orphan diseases.