Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset triplet repeat disorder that leads to dementia, ataxia, tremor, 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. Fragile X-associated tremor/ataxia syndrome affects less than 20% of female and about 50% of male carriers. In this review, Dr. Thomas of St. 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 various 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 healthcare costs. The pathomechanistic evidence of mitochondrial and RNA dysfunction and of a neurodevelopmental component to fragile X-associated tremor/ataxia syndrome is discussed.