The aim of this article is to describe neuroactive steroid research that has been focused on their physiological role in cognitive aging, an attractive new field in experimental gerontology. Neuroactive steroids have been recently proposed as biomarkers of cognitive aging, however, their specific functions have not yet been fully established. For instance, data emerging from human and animal studies suggest a complex relationship between neuroactive steroids and/or metabolites and cognitive processes during aging. Thus, a better knowledge of neuroactive steroid brain distribution and function could broaden our understanding of their physiological roles and lead to novel and more effective treatments for the management of age-related brain disorders. To this end, newly developed sensitive, specific, and accurate mass spectrometry assays may allow the quantification of neuroactive steroids in discrete brain regions and greatly contribute to unravel their role in age-related cognitive deficits.