Regulatory T cells (T_regs) are an immunosuppressive subpopulation of CD4⁺ T cells that are endowed with potent suppressive activity and function to limit immune activation and maintain homeostasis. These cells are identified by the hallmark transcription factor FOXP3 and the high-affinity interleukin-2 (IL-2) receptor chain CD25. T_regs can be recruited to and persist within the tumor microenvironment (TME), acting as a potent barrier to effective antitumor immunity. This chapter will discuss [i] the history and hallmarks of T_regs; [ii] the recruitment, development, and persistence of T_regs within the TME; [iii] T_reg function within TME; asnd [iv] the therapeutic targeting of T_regs in the clinic. This chapter will conclude with a discussion of likely trends and future directions.