Tumor immune cells shape the tumor immune microenvironment and play a key role in mediating control of cancer growth, and detection and elimination of transformed cells. Tumor-infiltrating lymphocytes (TILs) constitute the adaptive immune system population that recognizes and targets tumor-specific antigens through a polyclonal diverse T-cell receptor (TCR) clonality. In this chapter, we will describe the biology of TILs, the relationship between the immune system and tumor progression, and therefore, their importance in controlling tumor development. In addition, we will define terms such as immunosurveillance and cancer immunoediting, and we will summarize some examples in which the presence of infiltrating T cells has been described to be associated with prognosis, as well as to predict response to treatment during follow-up. In this chapter, we will review the characteristics of TILs that make their use interesting as an adoptive cell therapy strategy for immunotherapy, and we will review the history of TIL-based therapies up to the present day, when the US Food and Drug Administration (FDA) approved them in February 2024 to treat metastatic melanoma. However, this therapy has limitations such as the poor persistence of TILs in the infused patients, caused by the appearance of more exhausted phenotypes during the in vitro expansion phase required to prepare the treatment, and the poor specificity due to the growth of bystander T cells in the in vitro culture. In this chapter, we will review different strategies described in the literature to overcome the exhausted state of TILs and improve tumor-specific reactivity, such as redirecting T-cell targeting by introducing tumor-specific TCRs through genetic modification.