Atopic dermatitis can be a challenging disease to treat, often having a chronic or relapsing course. For patients with moderate to severe disease, it can result in significant morbidity and affect quality of life of patients or families. Current treatment can be associated with side effects or patient and caregiver concerns about use. Recent advances in the understanding of barrier defects and innate and adaptive immune systemic abnormalities in atopic dermatitis have provided potential new targets for therapeutic intervention. These advances include antimicrobial peptides, antistaphylococcal toxin strategies, Th2 cytokine inhibitors, and modulation of pruritus at the neuromediator level.