Acute skin and soft tissue infections are commonly encountered in the emergency room setting. The vast majority of patients with simple skin and soft tissue infections such as folliculitis, furunculosis, and carbuncles may generally be managed in the outpatient setting. Some of these patients may occasionally present with fever, chills, or inability to tolerate oral medications and warrant admission to the hospital. Patients with associated diabetes mellitus, acquired immunodeficiency syndrome, malignancies, and other forms of immune compromise are susceptible to severe skin and soft tissue infections. Life-threatening infections such as infection of deep spaces of the neck and necrotizing fasciitis presenting with minimal warning signs or symptoms are on occasion encountered in the emergency room and necessitate prompt diagnosis and the rapid initiation of surgical and medical therapy. Emergency room physicians should familiarize themselves with the diagnosis and management of such life-threatening illnesses. This article discusses skin and soft tissue infections commonly seen in emergency room setting.