Changes in the level and activity of brain-derived neurotrophic factor (BDNF) have been described in a number of neurodegenerative disorders since early 1990s. However, only in Huntington disease (HD) gain- and loss-of-function experiments have mechanistically linked these abnormalities with the genetic defect.In this chapter we will describe how huntingtin protein, whose mutation causes HD, is involved in the physiological control of BDNF synthesis and transport in neurons and how both processes are simultaneously disrupted in HD. We will describe the underlying molecular mechanisms and discuss pre-clinical data concerning the impact of the experimental manipulation of BDNF levels on HD progression. These studies have revealed that a major loss of BDNF protein in the brain of HD patients may contribute to the clinical manifestations of the disease. The experimental strategies under investigation to increase brain BDNF levels in animal models of HD will also be described, with a view to ultimately improving the clinical treatment of this condition.