We report a case of a 41-year-old black man who presented with chronic severe atopic dermatitis that only responded to oral corticosteroids. Failed treatments for this patient included topical corticosteroids, topical pimecrolimus, oral prednisone, oral antihistamines, azathioprine, and narrowband UV light therapy. Only oral corticosteroids provided significant relief. The patient had an immunoglobulin E (IgE) level of 7340 IU/mL (reference range, 0–100 IU/mL). He responded to a 12-week course of omalizumab, a humanized monoclonal anti-IgE antibody currently indicated for patients 12 years and older with moderate to severe persistent asthma. Our patient experienced no adverse events throughout the course of treatment. We suggest that omalizumab may have a role in the treatment of isolated atopic dermatitis in the adult population.