Infections attributable to Streptococcus are protean. These range from mild skin and soft tissue infections to life-threatening conditions like meningitis, endocarditis and toxic shock syndrome. In addition, streptococcal infection can be associated with noninfectious sequelae like rheumatic fever and post-streptococcal glomerulonephritis. There is a wide range of Streptococcus spp. causing human infections and different classifications of these organisms have been described, the most quoted being the Lancefield classification based on cell-wall antigens. Streptococci can be studied based on their species: S. pyogenes, S. pneumoniae, S. anginosus etc. or by the Lancefield classification group A, B, C, D etc. or by the clinical syndromes associated with these bacteria. This chapter will describe clinical syndromes associated with streptococcal skin and soft tissue infections ranging from mild: cellulitis and lymphangitis which can be treated in the out-patient setting, to more aggressive manifestations that require hospitalization (sepsis and toxic shock syndrome) and even surgery (necrotizing fasciitis, myositis and gangrene), It will also provide clues to clinical diagnosis as well as suggest recommendations for optimized management of these conditions.