Attention-deficit hyperactivity disorder (ADHD) and major depression are common ailments that can cause significant dysfunction throughout the life cycle. These two disorders may occur comorbidly. This case series describes 7 pediatric patients (aged 10-16 years) and 4 adults (aged 38-44 years) whose ADHD and comorbid major depression were treated in a naturalistic open clinical fashion. For all 11 patients, symptoms of major depression appeared to respond well to either fluoxetine or sertraline monotherapy. Using starting doses of fluoxetine 10 mg or sertraline 25 mg daily, we did not observe any adverse behavioral activation or clinical deterioration. However, no improvement in ADHD symptoms was observed in any patient during fluoxetine or sertraline monotherapy. Adjunctive treatment with a psychostimulant seemed necessary for chronic ADHD symptoms to be effectively addressed. The psychostimulants did not appear to provide observable antidepressant effects. With the exception of one adult who had a 20 mm Hg increase in diastolic pressure on methylphenidate monotherapy at 22.5 mg daily, the administration and coadministration of these agents were not associated with significant changes in blood pressure or heart rate. No patient developed suicidality, increased aggressiveness, mania, or other problematic side effects. This combination therapy was well tolerated and appeared to be effective in ameliorating both ADHD and depressive symptoms. These cases support previous suggestions that adjunctive treatment with psychostimulants might be a safe and effective intervention for children treated with fluoxetine or sertraline who have persistent ADHD symptoms and suggests that such combined treatment may be suitable for adults as well.