The use of corticosteroids, particularly high-potency steroids, for the treatment of various inflammatory conditions has been frequently associated with mood disturbance and psychosis. We report on a 12-year-old white boy treated with high doses of prednisone chronically for 7 years who presented with severe depression, irritability, violence, and psychosis. Sertraline was used to treat depressive as well as psychotic symptoms without the use of antipsychotics. This successful treatment of steroid-induced mood disorder and psychosis with a serotonin reuptake inhibitor is consistent with the literature describing a decrease in central and peripheral serotonin secretion due to steroids, as well as a possible relationship between mood and psychotic symptoms and low cerebrospinal fluid serotonin levels.