Acute febrile neutrophilic dermatosis, first described in 1964 by Robert Douglas Sweet, has been termed Sweet's syndrome. Classic Sweet's syndrome occurs in middle-aged women after a nonspecific infection of the respiratory or gastrointestinal tract. Raised erythematous plaques with pseudoblistering and occasionally pustules occur on the face, neck, chest, and extremities, accompanied by fever and general malaise. Involvement of the eyes, joints, and oral mucosa as well as internal manifestations of Sweet's syndrome in the lung, liver, kidneys, and central nervous system has been described. The disease is thought to be a hypersensitivity reaction. Parainflammatory (e.g., infections, autoimmune disorders, vaccination) and paraneoplastic (e.g., hemoproliferative disorders, solid malignant tumors) occurrence is found in approximately 25% of the cases and 2% are associated with pregnancy. Sweet's syndrome responds rapidly to systemic therapy with corticosteroids but recurs in about 25% of the cases. Alternative treatment modalities (e.g., potassium iodide, colchicine, dapsone, clofazimine, cyclosporine) have also been used. This article presents data from 38 patients with Sweet's syndrome and reviews its epidemiology, clinical spectrum, histologic features, laboratory results, differential diagnosis, pathogenic mechanisms, associated diseases, and treatment.