Cellulitis is a frequently diagnosed syndrome that causes considerable morbidity. For a subset of patients, recurrent bouts of infection impact their quality of life. Most cases are due to beta-hemolytic streptococci or Staphylococcus aureus. Inclusion of interdigital space (toe web) or mucosal (anal) swab cultures may increase the ability to define pathogens among patients with lower extremity cellulitis. The pathogenesis of cellulitis is complex, and more work is needed so that novel therapies and vaccines can be developed to improve treatment and prevention of this disorder.