Cell-mediated immunity seems to be critical for prevention and resolution of invasive S. aureus infections, but an imbalance in this immunity may also produce SIRS and death or an inadequate protective response with prolonged bacteremia and death. This dysregulation is likely at the heart of mortality and severe disease in humans. Anti-toxin antibodies may also come into play in reducing the severity of S. aureus infections, but these antibodies might also address superantigen-induced immune dysregulation. Thus, while changing intrinsic T cell responses may be therapeutically difficult, monoclonal antibodies against superantigens may have utility in addressing dysfunctional immune responses to S. aureus. The models above are hypotheses for examining, and potentially dramatically improving immune response to and safety of S. aureus vaccines.