Regulatory T cells (T(reg) cells) are a highly specialized subset of immune cells capable of specifically suppressing autoreactive cells and thereby preventing autoimmunity. T(reg) cells also play an important role in limiting the immune reaction in infectious diseases. In the context of malignancies, however, accumulation of T(reg) cells occurs in the tumor microenvironment. T(reg) cells have been associated with prevention of antitumor immunity and the evasion of efficient recognition of tumor antigens. In the past few years, several approaches have been developed to target and deplete T(reg) cells in the context of tumors. Overall, these interventions have the potential to eliminate T(reg) cells and thereby help strengthen antitumor immunity by vaccination.