Chikungunya is an arbovirus infection generally considered mild and characterized by fever and joint pain. During an exceptionally large-scale epidemic that affected the island of Réunion in 2005–2006, hospital physicians reported cases of mother-to-newborn viral transmission and clinical presentations differing from those typically described. An active surveillance system was established in February 2006 to describe atypical hospital-based forms of chikungunya on Réunion during the epidemic and to determine their frequency. A retrospective and prospective survey was conducted in the island’s four hospitals. Between March 2005 and April 2006, 44 mother-to-infant cases and 834 atypical cases—including 247 (30%) severe cases—as well as 68 deaths were recorded. Atypical forms accounted for 0.35% of chikungunya cases in the population. The most common clinical manifestations of atypical cases were gastrointestinal and neurological symptoms. Atypical cases occurred primarily among vulnerable individuals (young children, the elderly, and patients with underlying medical conditions). These results indicate the need to prioritize the development of prevention recommendations for these individuals and for pregnant women during a chikungunya epidemic. (R.A.)