Streptococcus suis is recognized as a major swine pathogen and an emerging zoonotic agent. Two large-scale outbreaks of severe S. suis epidemics occurred in China in 1998 and 2005 that posed serious concerns to public health and challenged the conventional conception that opportunistic infections of S. suis serotype 2 (SS2) in humans were only sporadic cases. An extensive, collaborative study on Chinese SS2 variants, which exhibit strong invasiveness and high pathogenicity, has resulted in the description of a new disease form of streptococcal toxic shock syndrome (STSS) and a putative pathogenicity island (termed 89K). The abbreviation of STSS is used for the severe disease caused by both Staphylococci and Streptococci. The main virulence factors involved in STSS caused by either Staphylococcus aureus or Streptococcus pyogenes consist of so-called superantigens or molecules that trigger a nonspecific, uncontrolled activation of T cells and massive cytokine release. However, although a collection of new virulence factors have been described, no superantigen candidates have been found for SS2 strains, implying that a different mechanism could be involved in the STSS form caused by SS2 variants.