The inflammatory response to transformed cells forms the cornerstone of natural or therapeutically-induced protective immunity to cancer. Regulatory T (Treg) cells are known for their critical role in suppressing inflammation, and therefore can antagonize effective anti-cancer immune responses. As such, Treg cells can play detrimental roles in tumour progression and in the response to both conventional and immune-based cancer therapy. Recent advances in our understanding of Treg cells reveal complex niche-specific regulatory programs and functions, which are likely to extrapolate to cancer. The regulation of Treg cells is reliant on upstream cues from haematopoietic and non-immune cells, which dictates their genetic, epigenetic, and downstream functional programmes. In this Review we will discuss how Treg cells are themselves regulated in normal and transformed tissues, and the implications of this crosstalk on tumour growth. This article is protected by copyright. All rights reserved.