| Regulatory T (T reg) cells suppress inflammation and regulate immune system activity. In patients with systemic or organ-specific autoimmune diseases or those receiving transplanted organs, T reg cells are compromised. Approaches to strengthen T reg cell function, either by expanding them ex vivo and reinfusing them or by increasing the number or capacity of existing T reg cells, have entered clinical trials. Unlike the situation in autoimmunity, in patients with cancer, T reg cells limit the antitumour immune response and promote angiogenesis and tumour growth. Their immunosuppressive function may, in part, explain the failure of many immunotherapies in cancer. Strategies to reduce the function and/or number of T reg cells specifically in tumour sites are being investigated to promote antitumour immunity and regression. Here, we describe the current progress in modulating T reg cells in autoimmune disorders, transplantation and cancer.