After several decades of seemingly decreasing virulence, streptococcal and staphylococcal infections have reemerged as a major source of morbidity and mortality. Within the past 2 decades, not only have well-established diseases such as rheumatic fever begun to reappear, but also many new entities, such as toxic shock syndrome, streptococcal toxic shock syndrome, recurrent toxin-mediated perineal erythema, and recalcitrant erythematous desquamating disorder have been described. Central to the renewed importance of these bacteria has been the production of circulating toxins, which often function as superantigens in causing the clinical manifestations, morbidity and mortality associated with these diseases. (J Am Acad Dermatol 1998;39:383-98.) Learning Objective: At the conclusion of this learning activity, participants should be familiar with the spectrum of toxin-mediated illnesses caused by streptococci and staphylococci. Participants should also have a greater understanding of toxins and superantigens as well as their role in these diseases.