OBJECTIVES: To review how the Hunter Outcome Survey (HOS), a physician-driven, multinational, observational survey supported by Shire HGT, has helped advance the understanding and management of Hunter syndrome — a rare, X-linked disorder of glycosaminoglycan (GAG) metabolism caused by deficiency of the enzyme iduronate-2-sulfatase. METHODS: HOS was established in 2005 to help understand the natural history of Hunter syndrome and the long-term safety and effectiveness of enzyme replacement therapy (ERT) with idursulfase. Data such as demographics, signs/symptoms, investigations, developmental milestones and laboratory test data are collected for patients with a confirmed diagnosis. Three working groups (Natural History, Cardiac and CNS) have been established to further data collection/interpretation in the respective fields. RESULTS: As of January 2009, 98 clinics across 23 countries have enrolled 642 patients. The first peer-reviewed paper, published in 2008, reported that the median ages of onset of symptoms and diagnosis were 1.5 and 3.5 years, respectively; the average height of Hunter children was normal up to approximately 9 years of age, following which it fell below the third percentile (Wraith et al., 2008). Other important findings include: by 6 years of age half of patients showed cardiovascular abnormalities (Wraith et al., 2007); the majority of patients developed airway involvement in childhood (Burton et al., 2008); and prior to diagnosis, the most common clinical symptoms were characteristic facial features, enlarged liver and spleen, hernia and otitis (Beck et al., 2007). CONCLUSIONS: In the short time HOS has been running, it has provided important real-world data on Hunter syndrome. Data analyses have identified the need for early diagnosis, to enable institution of appropriate therapeutic management. Through ongoing collaboration between participating physicians and working groups, HOS will continue to expand the evidence base of knowledge around Hunter Syndrome and be a valuable tool to evaluate the effectiveness of ERT and help optimize patient care.