Atopic dermatitis (AD) is a complex and heterogeneous inflammatory skin disorder with a profound symptom and lesional burden. Moderate-to-severe AD is particularly challenging to manage, as topical treatments are often inadequate and the systemic immunosuppressants are limited by concerns of toxicity and tolerability. Recent AD research has elucidated the mechanisms and immunologic factors involved in AD pathogenesis. These breakthroughs have led to the development of multiple therapeutic monoclonal antibodies that are directed against specific immunologic targets. This review provides an overview on the pathogenesis of AD as well as the rationale for the targets of various monoclonal antibodies. Additionally, this review explores the efficacy and safety of use for various monoclonal antibodies in the management of AD, as well as the potential role of these agents in the treatment of AD.