Huntington's disease (HD) is an inherited neurodegenerative disorder that affects about one in 10,000 individuals in North America. The genetic defect responsible for the disease is an expansion of a CAG repeat that encodes a polyglutamine tract in the expressed protein, huntingtin. The disease is characterized by involuntary movements, cognitive impairment, and emotional disturbance. Despite the widespread expression of huntingtin, the brains of HD patients show selective neuronal loss in the striatum and the deep layers of the cerebral cortex. Recent studies have shown that polyglutamine expansion causes huntingtin to aggregate, to accumulate in the nucleus, and to interact abnormally with other proteins. Several cellular and animal models for HD have revealed that intranuclear accumulation of mutant huntingtin and the formation of neuropil aggregates precede neurological symptoms and neurodegeneration. Intranuclear huntingtin may affect nuclear function and the expression of genes important for neuronal function, whereas neuropil aggregates may interfere with neuritic transport and function. These early pathological events, which occur in the absence of neurodegeneration, may contribute to the neurological symptoms of HD and ultimately lead to neuronal cell death.