Apart from finding novel compounds for treating Huntington's disease (HD) an important challenge at present consists in finding reliable read-outs or biomarkers that reflect key biological processes involved in HD pathogenesis. The core elements of HD biology, for example, HTT RNA levels or protein species can serve as biomarker, as could measures from biological systems or pathways in which Huntingtin plays an important role. Here we review the evidence for the involvement of mitochondrial biology in HD. The most consistent findings pertain to mitochondrial quality control, for example, fission/fusion. However, a convincing mitochondrial signature with biomarker potential is yet to emerge. This requires more research including in peripheral sources of human material, such as blood, or skeletal muscle.