Drug-induced acute febrile neutrophilic dermatosis, or Sweet's syndrome, is rare and, to our knowledge, has not previously been associated with clindamycin therapy. We describe a 47-year-old woman with type 2 diabetes mellitus and end-stage renal disease requiring hemodialysis who developed Sweet's syndrome after receiving oral and intravenous clindamycin for a tooth infection. After the clindamycin was discontinued, the patient's clinical symptoms resolved over several days. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of Sweet's syndrome and clindamycin therapy. Clinicians should be aware that Sweet's syndrome can occur with clindamycin treatment. Early recognition of this condition in conjunction with cessation of drug exposure, with or without antiinflammatory therapy, can produce complete recovery.