Ruxolitinib cream 1.5% was first approved by the US Food and Drug Administration (FDA) in 2011. Opzelura™ cream was introduced by Incyte Dermatology in 2021 for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients aged ≥ 12 years, whose clinical manifestations are not controlled with prescribed topical therapies, such as topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase-4 ( PDE4) inhibitors, or when such therapies are not advisable. Ruxolitinib is a Janus kinase (JAK) inhibitor that addresses inflammation in AD. It selectively inhibits JAK1 and JAK2, blocking JAK and activating signal transducer and activator of transcription (STAT), thereby interrupting the cytokine pathways responsible for cutaneous inflammation. The targeted downstream cytokines include Interleukin- 4 (IL-4), IL-13, IL-31, and cytokine thymic stromal lymphopoietin (TSLP), which play pivotal roles in the itching and inflammation experienced by AD patients. Ruxolitinib cream is directly applied as a thin layer over AD lesions twice daily up to 20% body surface area (BSA) using no more than 60 g per week. It can be used for up to 8 weeks on delicate or thin skin surfaces.