Polyglutamine (polyQ) diseases are a group of rare neurodegenerative disorders characterized by the abnormal expansion of a cytosine-adenine-guanine (CAG) trinucleotide repeat, resulting in the production of proteins with an expanded polyglutamine tract. The repeat expansions in these diseases take place in gene coding regions and produce protein with an anomalous structure and function. The expanded CAG/polyQ domains are identified as the primary drivers of neurodegeneration in this disease family. They mainly affect the central nervous system and are associated with progressive degeneration, dysfunction, and death of specific populations of neurons. At present, a total of nine polyQ disorders have been identified: Huntington's disease (HD); six spinocerebellar ataxias (SCA) types 1, 2, 3, 6, 7, 17; dentatorubral pallidoluysian atrophy (DRPLA); and spinal and bulbar muscular atrophy (SBMA) (Table ). Since the initial identification of the genetic basis of the polyQ diseases , thorough research has been performed to characterize the molecular basis of these disorders. PolyQ diseases exhibit inverse correlation between the number of CAG repeats and the age of onset of disease. The proteins involved in different polyQ diseases differ in their function and location within the cell. Moreover, different brain regions and neuronal cell subtypes are affected in each polyQ disease. Yet, a common feature of polyQ diseases is the radical deterioration of neurons in the specific regions of the brain, which cause impairment in vital functioning. Clinically, polyQ diseases exhibit threshold occurrences. Progressive pathological features are noticed once repeat numbers exceed disease-specific limits. Moreover, trinucleotide tracts are unstable and increase their length upon transmission to the next generations. A higher number of repeats bring about an earlier and more severe disease phenotype. All the polyQ diseases are inherited in an autosomal dominant way, except for SBMA, which is X-linked. Although animal models of polyQ disease for understanding pathology in humans and exploring disease-modifying therapies are available, there is neither a cure nor prevention for these diseases, and only symptomatic treatments for polyQ diseases currently exist. Long-term pharmacological treatment is so far unsatisfactory, possibly due to unwanted complications and falling drug efficacy. Cellular transplantation of stem cells may provide promising therapeutic avenues for restoration of the functions of degenerative and/or damaged neurons in polyQ diseases.