Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For non-responders to conventional therapies, AD can significantly reduce sleep quality and quality of life. AD pathogenesis is multifactorial and involves multiple immune pathways, with recent evidence of Th2, Th17, and Th22 axis attenuation in various AD endotypes and racial subtypes. Inhibition of the conserved Janus Kinase (JAK) signaling pathways represents a promising therapeutic avenue to reduce the activation of multiple pro-inflammatory mediators involved in AD pathogenesis. JAK inhibitors exist in both oral and topical forms with variable specificity for the receptor tyrosine kinases JAK1, JAK2, JAK3, and tyrosine kinase 2. Oral formulations include abrocitinib, upadacitinib, baricitinib, and gusacitinib and are most appropriate for patients with moderate-to-severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment modality to revolutionize the management of AD.