Changes in the level and activity of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), have been described in a number of neurodegenerative disorders, including Huntington’s disease, Alzheimer’s disease and Parkinson’s disease. It is only in Huntington’s disease, however, that gain-of-function and loss-of-function experiments have linked BDNF mechanistically with the underlying genetic defect. Altogether, these studies have led to the development of experimental strategies aimed at increasing BDNF levels in the brains of animals that have been genetically altered to mimic the aforementioned human diseases, with a view to ultimately influencing the clinical treatment of these conditions. In this presentation, I will focus on available data concerning changes in BDNF levels in HD cells, mice and human postmortem samples, describe the molecular evidence underlying this alteration, and review the data concerning the impact of the experimental manipulation of BDNF levels on HD progression. Finally, I will describe how the targeting of a specific mechanism that is responsible for the BDNF dysfunction could be a valid option to increase BDNF in HD.