Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increasing ability to evade neutralizing antibodies have emerged. Thus, earlier interest in defining the correlates of protection from infection, mainly mediated by humoral immunity, has shifted to correlates of protection from disease, which require a more comprehensive analysis of both humoral and cellular immunity. In this review, we summarized the evidence that supports the role of SARS-CoV-2-specific T cells induced by infection, by vaccination or by their combination (defined as hybrid immunity) in disease protection. We then analyzed the different epidemiological and virological variables that can modify the magnitude, function, and anatomical localization of SARS-CoV-2-specific T cells and their influence in the possible ability of T cells to protect the host from severe COVID-19 development.