Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease that affects children and adults. Until recently, the only Food and Drug Administration-approved systemic treatment option for patients with moderate-to-severe AD was systemic steroids, which are not recommended by current guidelines and are commonly associated with disease rebound. Instead, clinicians choose from several off-label immunosuppressants, which can have serious adverse effects. A significant number of these patients go untreated. Research on the immunopathogenesis of AD has paved the way for new, targeted, systemic therapies for moderate-to-severe AD. In early 2017, the Food and Drug Administration approved dupilumab for adults with moderate-to-severe AD whose disease is not adequately controlled with topical therapies. Although the national guidelines can be very helpful to clinicians, the process for updating them does not allow for timely incorporation of novel therapies. A steering committee of AD experts, including dermatologists, allergists, and a patient advocacy group representative, developed recommendations on the basis of a literature review and expert opinion to help clinicians understand how new therapies fit into the current treatment paradigm and to provide practical recommendations for assessing AD severity, treatment response, and treatment failure.