Regulatory T cells (Tregs) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. However, in the context of cancer their role is more complex, and they are thought to contribute to the progress of many tumours. As cancer cells express both self- and tumour-associated antigens, Tregs are key to dampening effector cell responses, and therefore represent one of the main obstacles to effective anti-tumour responses. Suppression mechanisms employed by Tregs are thought to contribute significantly to the failure of current therapies that rely on induction or potentiation of anti-tumour responses. This review will focus on the current evidence supporting the central role of Tregs in establishing tumour-specific tolerance and promoting cancer escape. We outline the mechanisms underlying their suppressive function and discuss the potential routes of Tregs accumulation within the tumour, including enhanced recruitment, in-situ or local proliferation, and de-novo differentiation. In addition, we review some of the cancer treatment strategies that act, at least in part, to eliminate or interfere with the function of Tregs. The role of Tregs is being recognized increasingly in cancer, and controlling the function of these suppressive cells in the tumour microenvironment without compromising peripheral tolerance represents a significant challenge for cancer therapies.