Traditional systemic agents used for the treatment of atopic dermatitis (AD) are associated with significant potential toxicities and often do not provide adequate therapeutic responses. Biologic agents hold promise for a more targeted and less toxic approach to AD systemic therapy. Patients with AD, however, may theoretically be at higher risk of developing IgE-mediated reactions to protein-based therapies. We performed a review of publications reporting the use of biologics in the treatment of AD. Of the 261 patients with AD identified who were exposed to a biologic therapy, no type-I immediate hypersensitivity reactions were reported. One infusion reaction occurred with infliximab and two patients had “mild respiratory difficulty” with interferon-gamma. Thrombocytopenia may occur at a higher rate than expected in patients treated with efalizumab. Combined, these data support the safety of biologics in the treatment of AD and the further development of new biologics for this population should be encouraged.