Polyglutamine disorders represent a group of neurodegenerative diseases caused by expanded CAG repeats within the coding regions of their respective genes, resulting in abnormally elongated polyglutamine tracts in the encoded proteins. These structural alterations promote protein misfolding, accumulation, and aggregation, leading to the formation of intracellular inclusions that impair neuronal function and ultimately drive progressive neurodegeneration. The polyglutamine disease family comprises Huntington’s disease, spinocerebellar ataxias types 1, 2, 3 (Machado–Joseph disease), 6, 7, and 17, dentatorubral–pallidoluysian atrophy, and spinal and bulbar muscular atrophy (Kennedy’s disease). Most polyglutamine disorders follow an autosomal dominant mode of inheritance, with spinal and bulbar muscular atrophy representing the only X-linked exception. This chapter focuses on models of Huntington’s disease, dentatorubral–pallidoluysian atrophy, and spinal and bulbar muscular atrophy.