Rare diseases have a low prevalence and a high level of clinical complexity, which makes their diagnosis very difficult. It is therefore not surprising that a high percentage of such cases have to be referred to specialised clinical centres and, ultimately, to non-diagnostic case programmes. SpainUDP is one such programme, created by the Institute for Research on Rare Diseases (Instituto de Salud Carlos III) in an attempt to respond to the large number of consultations received at this centre on undiagnosed cases. SpainUDP offers a multidisciplinary approach to patients who have been seeking a diagnosis for their disease for a long time without getting a clear answer. The procedure used at SpainUDP to try to obtain a diagnosis for these patients is based on the exhaustive and individualised study of each case, the use of the latest technological advances in the field of genomics and the establishment of international information exchange systems.