Introduction: Atopic dermatitis is a chronic, relapsing, pruritic inflammatory skin disease. Both skin barrier defects and abnormal immune reactions contribute to this complex disease. Current therapeutic guidelines recommend the use of moisturizers, good skin care and allergen avoidance as the first-line approach. In patients who do not respond well to these measures, topical corticosteroids, calcineurin inhibitors, and, in severe cases, systemic immunosuppressive agents are mostly used. Areas covered: This review summarizes the patent applications for small-molecule compounds for the treatment of atopic dermatitis from 2009 to date. These substances include compounds targeting the skin barrier (filaggrin production promoters, filaggrin breakdown products and compounds improving stratum corneum lipid barrier including pseudoceramides), anti-inflammatory compounds (PDE4/7 inhibitors, CRTH2 inhibitors, chemokine receptor antagonists, inhibitors of chymase and other) and compounds specifically targeting itch (TRP agonists, opioid ligands, serotonin 7 and histamine 4 antagonists). Expert opinion: Recent advances in understanding the pathogenic mechanisms of atopic dermatitis have created a strong rationale for the design of targeted therapeutics. Most emerging compounds target inflammation and/or pruritus, probably because of the broader therapeutic utility of such compounds. Specific skin barrier-corrective therapies are much fewer but bear strong potential to actually prevent inflammation.