Parkinson's (PD) and Huntington's disease (HD) are chronic neurodegenerative conditions of the brain with a variety of clinical presentations including a disorder of movement and a range of nonmotor deficits. HD is genetic in origin and the causative gene and protein known, namely mutant Huntingtin, which leads to widespread early neuronal dysfunction and death throughout the brain. In contrast, the etiology of sporadic PD is unknown, and the pathology targets the nigrostriatal dopaminergic neurons with the formation of α-synuclein positive Lewy bodies. In both diseases, the ability to accurately diagnose the disease in the early stages and monitor progression over time remains a major challenge given the majority of the pathology is sited deep within the CNS. This challenge has gained extra significance as the development of disease-modifying drugs starts to emerge into the clinic. To this end, there is a need to find biomarkers that will help in the accurate diagnosis of the disease and/or prediction of its clinical onset as well as biomarkers that are able to faithfully track disease progression independent of any symptomatic effects of any therapies. In addition, these same markers may also help stratify each of these heterogeneous disorders into specific subtypes that share particular clinical and pathological characteristics.