T cell exhaustion is a state of dysfunction in T cells during chronic infections and cancer, characterized by loss of effector function, expression of multiple inhibitory receptors, and altered transcriptional programs. This state impairs immune control of persistent pathogens and tumors but can be reversed by targeting pathways such as PD1 and CTLA4, which are overexpressed in exhausted T cells. Exhausted T cells retain some functional capacity but are ineffective in eliminating pathogens or tumors. Recent advances have provided molecular insights into the mechanisms of T cell exhaustion, including the role of inhibitory receptors, co-stimulatory pathways, and soluble mediators like IL-10 and TGFβ. These findings highlight the importance of understanding the complex interplay between T cell exhaustion and immune regulation. The development of exhausted T cells is influenced by persistent antigen exposure, chronic inflammation, and interactions with other immune cells such as regulatory T cells. The transcriptional and epigenetic changes in exhausted T cells, including the expression of inhibitory receptors and altered use of transcription factors, contribute to their dysfunction. The distinction between exhausted T cells and other dysfunctional T cells, such as senescent or anergic T cells, is important for understanding their unique characteristics. The identification of distinct subsets of exhausted T cells, defined by markers such as PD1, CD44, and transcription factors like T-bet and EOMES, has provided insights into their lineage dynamics and maintenance. The role of homeostatic cytokines, such as IL-2 and IL-7, in supporting the survival and function of exhausted T cells is also critical. Overall, the study of T cell exhaustion has significant implications for the development of immunotherapies targeting chronic infections and cancer.T cell exhaustion is a state of dysfunction in T cells during chronic infections and cancer, characterized by loss of effector function, expression of multiple inhibitory receptors, and altered transcriptional programs. This state impairs immune control of persistent pathogens and tumors but can be reversed by targeting pathways such as PD1 and CTLA4, which are overexpressed in exhausted T cells. Exhausted T cells retain some functional capacity but are ineffective in eliminating pathogens or tumors. Recent advances have provided molecular insights into the mechanisms of T cell exhaustion, including the role of inhibitory receptors, co-stimulatory pathways, and soluble mediators like IL-10 and TGFβ. These findings highlight the importance of understanding the complex interplay between T cell exhaustion and immune regulation. The development of exhausted T cells is influenced by persistent antigen exposure, chronic inflammation, and interactions with other immune cells such as regulatory T cells. The transcriptional and epigenetic changes in exhausted T cells, including the expression of inhibitory receptors and altered use of transcription factors, contribute to their dysfunction. The distinction between exhausted T cells and other dysfunctional T cells, such as senescent or anergic T cells, is important for understanding their unique characteristics. The identification of distinct subsets of exhausted T cells, defined by markers such as PD1, CD44, and transcription factors like T-bet and EOMES, has provided insights into their lineage dynamics and maintenance. The role of homeostatic cytokines, such as IL-2 and IL-7, in supporting the survival and function of exhausted T cells is also critical. Overall, the study of T cell exhaustion has significant implications for the development of immunotherapies targeting chronic infections and cancer.