CD4+ CD25+ T cells are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models revealed that Treg are potent inhibitors of an anti-tumor immune response. Treg are expanded in human cancer. Currently, a variety of strategies for the induction of a specific anti-tumor immune response are tested in preclinical and clinical settings. Biochemical strategies modifying and/or depleting Treg in cancer patients for an enhancement of vaccine-based therapeutic concepts will be discussed in detail in this review.