Increasing age has been associated with an insufficient protection following vaccination and an increased incidence and severity of infectious diseases. The predicted acceleration of global population aging will accentuate the need to understand the mechanisms that drive the age-related decline of the immune system and to, eventually, identify strategies to lower the burden of infectious diseases in elderly people. One type of immune cell appears to be most dramatically affected by the aging process: T lymphocytes. Age-related changes of the bone marrow and the thymus microenvironment lead to a decreased thymic output of functional, naïve T lymphocytes. As T lymphocytes are key players of the adaptive immune system, this research topic will summarize our current understanding on how aging affects the microenvironmental niches and molecular networks that are important for the generation, survival and function of naïve, memory and effector T lymphocytes. This research topic will also address the impact of aging on the different T lymphocyte lineages, such as regulatory T cells and Th17 cells and how age-related changes of the microenvironment affect organ- and tissue-resident memory T lymphocytes. Eventually, the identification of a set of markers for immunosenescence would facilitate the design and application of more specific therapies and improved vaccines and vaccination strategies for elderly people, thereby increasing life and health span.