Heat-stable enterotoxins are the most notable virulence factors associated with Staphylococcus aureus, a common pathogen associated with serious community and hospital acquired diseases. Staphylococcal enterotoxins (SEs) cause toxic shock-like syndromes and have been implicated in food poisoning. But SEs also act as superantigens that stimulate T-cell proliferation, and a high correlation between these activities has been detected. Most of the nosocomial S. aureus infections are caused by methicillin-resistant S. aureus (MRSA) strains, and those resistant to quinolones or multiresistant to other antibiotics are emerging, leaving a limited choice for their control. This review focuses on these diverse roles of SE, their possible correlations and the influence in disease progression and therapy.