Fragile X-associated tremor/ataxia syndrome is a late-onset triplet repeat disorder that leads to dementia, parkinsonism, and neuropathy. Its cause is a restricted triplet repeat expansion mutation in the fragile X mental retardation gene (FMR1), whereas a larger expansion results in fragile X syndrome A in children. In this clinical article, Dr. Thomas of Saint Louis University and Dr. Singh of the University of Missouri - Columbia, focus on fragile X-associated tremor/ataxia syndrome and its relation to fragile X syndrome A. Fragile X-associated tremor/ataxia syndrome illustrates the importance of obtaining a comprehensive family history that is not limited to clinical question of the patient in question. Fragile X-associated tremor/ataxia syndrome is in the differential diagnosis in patients with varying combinations of the above symptoms with or without a family history of mental retardation. Some estimates suggest that as many as 1 in 3000 men above 50 years of age may develop fragile X-associated tremor/ataxia syndrome; such numbers would signify a great impact on health care costs. The pathomechanistic evidence of mitochondrial and RNA dysfunction and of a neurodevelopmental component to fragile X-associated tremor/ataxia syndrome is discussed.