Cellulitis can be a diagnostic and therapeutic challenge. Based on a systematic review that identified 123 pertinent articles, Raff and Kroshinsky summarize the evidence relating to the epidemiology, pathophysiology, microbiology, diagnosis, and treatment of cellulitis. Cellulitis is common and the diagnosis is based primarily on patient history and physical examination findings. Antibiotic treatment of uncomplicated cellulitis should be directed against Streptococcus and methicillin-sensitive Staphylcoccus aureus. Methicillin-resistant S aureus should be considered in high-risk patient populations.