Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. When inflammation and aging affect the brain, we use the term neuro-inflammaging. In this review, we focused on the neuro-inflammatory process typical of advanced ages and the related psychopathological symptoms, with particular attention to understanding the immune-pathogenetic mechanisms involved and the potential use of immunomodulatory drugs in the control of clinical psychological signs. Inflammation and CNS were demonstrated being intimately linked in the neuro-inflammatory loop. IL-1, IL-6, TNF-a, COX and PGE are only partially responsible. BBB permeability and the consequent oxidative stress resulting from tissue damage make the rest. Some authors elaborated the "theory of cytokine-induced depression". Inflammation has a crucial role in the onset symptoms of psychopathological diseases as it is capable of altering the metabolism of biogenic monoamines involved in their pathogenesis. In recent years, NSAIDs as an adjunct therapy in the treatment of relevant psychopathological disorders associated with chronic inflammatory conditions demonstrated their efficacy. Additionally, novel molecules have been studied, such as adalimumab, infliximab, and etanercept showing antidepressant and anxiolytic promising results. However, we are only at the beginning of a new era characterized by the use of biological drugs for the treatment of inflammatory and autoimmune diseases, and this paper aims to stimulate future studies in such a direction.