Advances in our understanding of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T(Regs)) enabled the characterization of their activities in maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. Ironically, an effective action of these cells during tumor development can limit beneficial responses by suppressing immunity and limiting antitumor resistance, whereas one of the main functions of the immune system is to eliminate malignant cells. During the last years, the immunological role, mechanism of action, and clinical importance of these cells were profoundly characterized and the relationship between this subset of lymphocytes and cancerous cells arises as a key factor that influences tumor development. Recent insights obtained from clinical studies and experimental mouse models expand our perception of the potential role of T(Regs) in cancer treatment. In this review we describe the basic mechanisms of T(Reg) origin and differentiation, their potential role in cancer, as well as the future perspectives concerning the modulation of these cells as a potential approach for anticancer strategies.