Metabolic adverse effects such as hyperglycemia, alterations in insulin sensitivity, and weight gain are known to be potential complications of atypical antipsychotic therapy. In certain cases, hyperglycemia may be so profound that diabetic ketoacidosis (DKA) or hyperosmolar coma may result. Aripiprazole, approved by the United States Food and Drug Administration in 2002, appears to have fewer metabolic adverse effects than other atypical antipsychotics. We describe a 44-year-old man with no personal or family history of diabetes mellitus who was prescribed aripiprazole for schizoaffective disorder. Two weeks after starting this therapy, the patient developed DKA, which was corrected with insulin therapy and aggressive hydration. According to the Naranjo adverse drug reaction probability scale, aripiprazole was the probable trigger of his DKA. An exhaustive search for other causes of DKA was unrevealing. Administration of aripiprazole or any other atypical antipsychotic should be terminated when impaired glucose tolerance is suspected. Vigilance regarding the potential adverse effects of this class of drugs, including new agents such as aripiprazole, is crucial to preventing potentially life-threatening complications of hyperglycemia.