Polyglutamine diseases are inherited neurodegenerative diseases caused by the expansion of polyglutamine tract in the disease causing gene products. Studies of polyglutamine disease patients and transgenic mice have revealed that nuclear inclusions formed by the disease protein are a common pathological feature of these diseases. The finding that nuclear inclusions are ubiquitinated raises the possibility that alterations in the major intracellular system for degrading proteins, the ubiquitin-proteasome pathway, may be involved in the pathogenesis of polyglutamine diseases. Perturbations in proteasome function are associated with altered expression levels of stress-response or heat shock proteins. Heat shock proteins function as molecular chaperones, which recognize and renaturate misfolded protein (aggregate). In this article, we review the role of chaperones in the development of polyglutamine diseases. Overexpression of chaperones reduces aggregate formation and suppresses apoptosis in several polyglutamine disease models including spinal and bulbar muscular atrophy. These facts indicate that chaperones may be one of the key factors in the development of polyglutamine disease, and suggest that increasing expression level or enhancing the function of chaperones will provide an avenue for the treatment of polyglutamine disease.