Toxic shock syndrome (TSS) is a potentially fatal illness caused by infection with the bacterium Staphylococcus aureus. TSS toxin-1 (TSST-1) contains a T-cell epitope with specificity for human V-beta-2. Binding of TSST-1 to the human major histocompatibility complex and T cell receptors activates T cells and triggers the secretion of high amounts of inflammatory cytokines, leading to TSS and potentially death. During this process, CD4+ T cells are inhibited by TSST-1, while regulatory T cells are increased. This suggests a protective immune response by the body in TSS. Thus, TSST-1 can trigger both, an inflammatory response that attacks the body and a protective response. In this review, we discuss the interaction between TSST-1 and T lymphocytes in TSS.