This article presents a historical perspective of foundational studies utilizing near-infrared spectroscopy (NIRS) to measure the hemodynamics, oxygenation, and activation of the human brain cortex during cognitive tasks, called functional NIRS (fNIRS). It discusses studies representative of the diagnostic power and potential that fNIRS has shown for providing increased understanding of cognitive changes with aging and dementia. It concludes by discussing challenges that continue to confront the implementation of NIRS and fNIRS in clinical and translational research, in particular, the challenges to measure cognitive function and impairment in aged, chronically ill, and fragile subjects with or without dementia. It is written specifically in memoriam, honoring Britton Chance, therefore papers authored by him and his collaborative research family are weighted to illustrate the significant foundation and legacy he has left to this world.