Rare metabolic diseases are chronic, progressive, present frequently with a life-threatening course and may result in severe handicaps. They demand high diagnostic and therapeutic standards and efforts from physicians and patients. The challenge for society and health systems in dealing with patients affected by one of these diseases is to offer comprehensive service by a multi-professional team of specialists and evidence-based as well as economic (i.e. necessary, sufficient and effective) treatment. Patients and families should be treated in specialized metabolic centres guaranteeing continuous improvement of the scientific and clinical principles of treatment, standardized outcome evaluation, strict quality assurance as well as optimal psychosocial care and counselling. Networking of national and international metabolic centres seems imperative for clinical research in the field of rare metabolic diseases in order to provide adequate sample sizes and to yield substantial results.