A diverse array of human infection is caused by Staphylococcus aureus and Streptococcus pyogenes, from minor skin and soft tissue infections to disseminated, invasive disease associated with significant morbidity and mortality. The term toxic shock syndrome is used to describe serious, life-threatening illness associated with particular strains of Staphylococcus aureus and Streptococcus pyogenes that demonstrate the ability to excrete a variety of toxins capable of inducing rash, shock, focal pyogenic, and/or necrotizing infection and multi-organ system failure. It has been my experience that in many cases of toxic shock syndrome, early clinical clues are missed, leading to unnecessary delays in diagnosis and initiation of specific anti-staphylococcal and streptococcal antimicrobial therapy. The key to effective management of toxic shock syndrome lies in the early recognition of telltale symptoms and physical findings so that treatment interventions can be initiated early enough to have a significant impact on the considerable morbidity and mortality associated with this disease.