The peripheral immune system can promote either immunity or tolerance when presented with new antigens. Current knowledge withholds that populations of suppressor or regulatory T cells (Treg cells) constitute a pivotal mechanism of immunological tolerance. The potential role of malfunctioning Treg cells in chronic inflammatory immune and auto-immune diseases is well-documented. Learning how to successfully manipulate Treg responses could result in more effective vaccines and immunomodulators. We have already shown that Thymosin α1 (Tα1), a naturally occurring thymic peptide first described and characterized by Allan Goldstein in 1972, by modulating signals delivered through innate immune receptors on dendritic cells, affects adaptive immune responses via modulation of Th cell effector and regulatory functions. We will discuss recent molecular mechanisms underlying the ability of Tα1 to activate or inhibit immune responses.