Two decades ago, researchers identified that a CAG expansion mutation in the 
huntingtin (HTT) gene was involved in the pathogenesis of Huntington's disease 
(HD). However, since the identification of the HTT gene, there has been no 
advance in the development of therapeutic strategies to prevent or reduce the 
progression of HD. With the recent advances in stem cell biology and human cell 
reprogramming technologies, several novel and exciting pathways have emerged 
allowing researchers to enhance their understanding of the pathogenesis of HD, 
to identify and screen potential drug targets, and to explore alternative donor 
cell sources for cell replacement therapy. This review will discuss the role of 
compensatory neurogenesis in the HD brain, the use of stem cell-based therapies 
for HD to replace or prevent cell loss, and the recent advance of cell 
reprogramming to model and/or treat HD. These new technologies, coupled with 
advances in genome editing herald a promising new era for HD research with the 
potential to identify a therapeutic strategy to alleviate this debilitating 
disorder. Stem Cells 2018;36:146-160.