Background: The management of people affected by age-related neurological disorders requires the adoption of targeted and cost-effective interventions to cope with chronicity. Therapy adaptation and rehabilitation represent major targets requiring long-term follow-up of neurodegeneration or, conversely, the promotion of neuroplasticity mechanisms. However, affordable and reliable neurophysiological correlates of cerebral activity to be used throughout treatment stages are often lacking. The aim of this systematic review is to highlight actual applications of functional Near-Infrared Spectroscopy (fNIRS) as a versatile optical neuroimaging technology for investigating cortical hemodynamic activity in the most common chronic neurological conditions. Methods: We reviewed studies investigating fNIRS applications in Parkinson’s Disease (PD), Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) as those focusing on motor and cognitive impairment in ageing and Multiple Sclerosis (MS) as the most common chronic neurological disease in young adults. The literature search was conducted on NCBI PubMed and Web of Science databases by PRISMA guidelines. Results: We identified a total of 63 peer-reviewed articles. The AD spectrum is the most investigated pathology with 40 articles ranging from the traditional monitoring of tissue oxygenation to the analysis of functional resting-state conditions or cognitive functions by means of memory and verbal fluency tasks. Conversely, applications in PD (12 articles) and MS (11 articles) are mainly focused on the characterization of motor functions and their association with dual-task conditions. The most investigated cortical area is the prefrontal cortex, since reported to play an important role in age-related compensatory mechanism and neurofunctional changes associated to these chronic neurological conditions. Interestingly, only 9 articles applied a longitudinal approach. Conclusion: The results indicate that fNIRS is mainly employed for the cross-sectional characterization of the clinical phenotypes of these pathologies, whereas data on its utility for longitudinal monitoring as surrogate biomarkers of disease progression and rehabilitation effects are promising but still lacking.