Dermatologists frequently are consulted in the evaluation and management of the patient with cellulitic-appearing skin. For routine cellulitis, the clinical presentation and patient symptoms are usually sufficient for an accurate diagnosis. However, when the clinical presentation is somewhat atypical, or if the patient fails to respond to appropriate therapy for cellulitis because of routine bacterial pathogens, the differential diagnosis should be rapidly expanded. We discuss the approach to the patient with presumed cellulitis, with an emphasis on the differential diagnosis of cellulitis in both the immunocompetent and immunucompromised patient.