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Atopic dermatitis is a highly prevalent chronic, immune-mediated inflammatory skin disease with a significant burden on patients, families and healthcare systems. This article presents recommendations developed by the Atopic Dermatitis Group of the Portuguese Society of Dermatology and Venereology addressing several clinical questions that arise in the management and care of moderate-to-severe atopic dermatitis with biologic agents and Janus kinase (JAK) inhibitors based on the available evidence. The recommendations were generated after a thorough evaluation of existing guidelines on the treatment of atopic dermatitis, publications concerning new biologics and JAK inhibitors not yet incorporated into existing guidelines, and expert-based recommendations. It also includes considerations on atopic dermatitis severity, indications for initiating biologic agents and JAK inhibitors, parameters to be considered in the treatment choice, in particular treatment goals, and recommendations for the use, screening and monitoring of these therapies.