This article describes the multiple escape mechanisms used by tumor cells to avoid T-cell–mediated recognition and destruction. The discussion focuses on escape mechanisms that may result from changes at the level of TA-specific cytotoxic T lymphocytes and tumor cells in the tumor microenvironment. Specifically, we discuss the negative impact of regulatory T cells and T-cell apoptosis on the tumor antigen–specific cytotoxic T lymphocyte response. We also discuss changes in the expression of histocompatibility antigens by tumor cells, which may affect tumor cell–immune cell interactions.