Currently the only approved drug available for the systemic therapy of atopic dermatitis is cyclosporine; however, based on current data from published studies, azathioprine, methotrexate, and mycophenolate mofetil or mycophenolic acid can be administered off-label. Some biologics on the market that have been approved for other indications (ustekinumab, rituximab, tocilizumab) have been successfully used in a few patients with atopic dermatitis. The world's first prospective controlled studies with the biologic human anti-IL4R antibody dupilumab for the indication "atopic dermatitis" were published in 2014. These motivated (1) to extend the studies to dupilumab and (2) to clinically test antagonization of other target molecules of TH2 polarized, atopic inflammation, e.g., IL-13, IL-31, IL-22, TSLP, and CRTH2. A number of clinical trials are currently recruiting in this area and will provide interesting new insights for future therapeutic approaches in atopic dermatitis.