Atopic dermatitis (AD) is moving beyond one-size-fits-all topical therapy. Over the last two years, large clinical programs and reviews have shown that targeted therapies — monoclonal antibodies (biologics) and small-molecule Janus kinase inhibitors (JAKis) — can reduce inflammation, itch, and flares in moderate-to-severe AD with tolerable safety profiles for many patients. These agents work by blocking specific immune pathways (for example, IL-4/IL-13 signaling targeted by dupilumab) and are reshaping treatment algorithms for adults and adolescents who fail topical measures. Importantly, researchers are defining molecular endotypes of AD (distinct immunologic signatures) so clinicians can match the right drug to the right patient — the essence of precision dermatology. Real-world registries and long-term extension studies now support durable efficacy and improvements in quality of life, while newer topical barrier-repair strategies and adjunctive nonpharmacologic measures (education, emollient regimens) remain essential. As with any novel therapy, cost, access, and careful monitoring for side effects (including rare infections and lab abnormalities with systemic agents) remain practical considerations. Clinicians should combine biologic/JAK therapy decisions with patient goals and safety screening to optimise outcomes.