Huntington’s disease is a progressive neurodegenerative disease resulting from a genetic mutation and is characterized by cognitive disability as well as motor disorders. In Huntington’s disease, cognitive disability may develop before motor symptoms appear, and this situation may worsen as the disease progresses. Impairments in cognitive disability include impairments in executive functions, memory, processing speed, and attention. In addition, neuroinflammation that develops in the brain in Huntington’s disease plays an important role in the exacerbation of cognitive decline as an effective factor in the pathogenesis of the disease. Neuroinflammation in Huntington’s disease is driven by immune cells in the brain such as microglia and astrocytes. Mutant Huntingtin (mHTT) protein, which is essential in the basis of Huntington’s disease, accumulates in the brain and may trigger a chronic inflammatory response. It is predicted that inflammation developing in the brain may be an important factor that accelerates cognitive decline in Huntington’s disease by suppressing neurogenesis. Since cognitive disability in Huntington’s disease is associated with mHTT protein effects and chronic neuroinflammatory processes in the brain, the development of therapeutic strategies targeting inflammatory pathways in this disease is extremely important to prevent or slow down cognitive decline. Therefore, the aim of this entry is to provide information about the pathophysiology of Huntington disease as well as to examine in detail the relationship between cognitive disability and inflammation in this disease.