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Cellulitis is an infection of the deep dermis and subcutaneous tissue, presenting with expanding erythema, warmth, tenderness, and swelling. Cellulitis is a common global health burden, with more than 650 000 admissions per year in the United States alone.In the United States, an estimated 14.5 million cases annually of cellulitis account for $3.7 billion in ambulatory care costs alone. The majority of cases of cellulitis are nonculturable and therefore the causative bacteria are unknown. In the 15% of cellulitis cases in which organisms are identified, most are due to β-hemolytic Streptococcus and Staphylococcus aureus. There are no effective diagnostic modalities, and many clinical conditions appear similar. Treatment of primary and recurrent cellulitis should initially cover Streptococcus and methicillin-sensitive S aureus, with expansion for methicillin-resistant S aureus (MRSA) in cases of cellulitis associated with specific risk factors, such as athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, those with prior MRSA exposure, and intravenous drug users. Five days of treatment is sufficient with extension if symptoms are not improved. Addressing predisposing factors can minimize risk of recurrence. The diagnosis of cellulitis is based primarily on history and physical examination. Treatment of uncomplicated cellulitis should be directed against Streptococcus and methicillin-sensitive S aureus. Failure to improve with appropriate first-line antibiotics should prompt consideration for resistant organisms, secondary conditions that mimic cellulitis, or underlying complicating conditions such as immunosuppression, chronic liver disease, or chronic kidney disease.