Chronic antigenic stimulation leads to gradual accumulation of late‐differentiated, antigen‐specific, oligoclonal T cells, particularly within the CD8⁺ T‐cell compartment. They are characterized by critically shortened telomeres, loss of CD28 and/or gain of CD57 expression and are defined as either CD8⁺CD28⁻ or CD8⁺CD57⁺ T lymphocytes. There is growing evidence that the CD8⁺CD28⁻ (CD8⁺CD57⁺) T‐cell population plays a significant role in various diseases or conditions, associated with chronic immune activation such as cancer, chronic intracellular infections, chronic alcoholism, some chronic pulmonary diseases, autoimmune diseases, allogeneic transplantation, as well as has a great influence on age‐related changes in the immune system status. CD8⁺CD28⁻ (CD8⁺CD57⁺) T‐cell population is heterogeneous and composed of various functionally competing (cytotoxic and immunosuppressive) subsets thus the overall effect of CD8⁺CD28⁻ (CD8⁺CD57⁺) T‐cell‐mediated immunity depends on the predominance of a particular subset. Many articles claim that CD8⁺CD28⁻ (CD8⁺CD57⁺) T cells have lost their proliferative capacity during process of replicative senescence triggered by repeated antigenic stimulation. However recent data indicate that CD8⁺CD28⁻ (CD8⁺CD57⁺) T cells can transiently up‐regulate telomerase activity and proliferate under certain stimulation conditions. Similarly, conflicting data is provided regarding CD8⁺CD28⁻ (CD8⁺CD57⁺) T‐cell sensitivity to apoptosis, finally leading to the conclusion that this T‐cell population is also heterogeneous in terms of its apoptotic potential. This review provides a comprehensive approach to the CD8⁺CD28⁻ (CD8⁺CD57⁺) T‐cell population: we describe in detail its origins, molecular and functional characteristics, subsets, role in various diseases or conditions, associated with persistent antigenic stimulation.