The tumor microenvironment consists of numerous and diverse immune cells many of which act to suppress the immune system response against cancer cells. Regulatory T cells (Tregs) perform a key role in mediating this immunosuppressive response via a variety of mechanisms. Tregs express FoxP3, CD4, and CD25 and they develop either in the thymus or differentiate in the periphery from naive T cells. To this day, Treg infiltration has been shown to have prognostic significance in many solid tumors. The tumor microenvironment and the role of Tregs in soft tissue sarcomas have only recently begun to unfold. In this chapter, we review the characteristics of Tregs, the various mechanisms of their functions in the tumor microenvironment as well as the prognostic significance they pose in malignant tumors and soft tissue sarcomas in particular.