Atopic dermatitis is the most common inflammatory skin disorder of children and has been shown to affect approximately 7% of adults as well. Therapy has long focused on barrier repair, topical corticosteroids and, in severe cases, broad systemic immunosuppressant medications. Attention has recently focused on developing therapeutics that target the underlying pathogenesis, thought to be a combination of barrier abnormalities, immune alterations, and environmental influences. How these factors interplay and which can best be targeted to reduce severity, prevent disease or disease exacerbations, or even lower the risk of developing comorbidities are active areas of investigation. Furthermore, it is clear that atopic dermatitis is a heterogeneous group of disorders, and that sub-phenotyping will be important for determining individual prognosis, risks, and response to therapeutics as we move towards precision medicine. The range of new therapies (from Th2-targeting to JAK inhibitors to targeting other immune pathways to PDE4 inhibition) will be discussed.