Sepsis is denoted as a complex syndrome that results from a serious infection followed by amplified and dysregulated inflammatory response. The complex immune response associated with sepsis results in a high rate of morbidity and mortality, despite substantial basic science and clinical advances. Recently, accumulating evidence have demonstrated that regulatory T cells (Tregs) play important roles in suppression of immune response, as demonstrated by the number increase and functional enhancement following the onset of severe sepsis or septic shock. This article reviews recent advances in understanding the potential role of Tregs in the pathophysiology of septic response, as well as implications in the development of novel therapeutic strategies for improving the clinical outcome of patients with severe injury and subsequent septic complications.