T cells are the master regulators of adaptive immune responses and maintenance of their tolerance is critical to prevent autoimmunity. However, in the case of carcinogenesis, the tumor microenvironment aids T-cell tolerance, which contributes to uncontrolled tumor growth. Recently, there has been significant progress in understanding the intrinsic extracellular (positive and negative costimulatory molecules on APCs) and intracellular mechanisms (E3 ubiquitin ligases, transcriptional and epigenetic repressors), as well as extrinsic mechanisms (Tregs and tolerogenic dendritic cells) that are required for the implementation and maintenance of T-cell tolerance. Ultimately, understanding and manipulating T-cell tolerance will help to break the tolerance state in cancer.