One mechanism of cancer immune evasion is the suppression of anti-tumor immunity by immunoregulatory T cells. Recent studies of these cells, especially CD4(+)CD25(+) T cells and NKT cells, have revealed molecular and cellular mechanisms of immunosuppression. Mouse studies have shown that either removing immunoregulatory T cells or blocking an immunoregulatory pathway induced by such cells unmasks natural tumor immunosurveillance and improves responses to cancer vaccines. Studies of the corresponding T-cell populations in human cancer patients support a similar role for immunoregulatory T cells in immunosuppression, implying that blocking immunoregulatory T-cell activity might improve the efficacy of tumor vaccines or the immunotherapy of cancer.