Recent investigations have shown atopic dermatitis (AD) results from the interplay of epidermal barrier defects, immune dysfunction and environmental triggers. These discoveries teach the importance of addressing all of these factors in treating patients. The barrier issues remind us of the need for moisturizers, especially after bathing, to replenish lipids and decrease water loss. Addition of dilute sodium hypochlorite (bleach) to bathwater often improves the dermatitis of children with moderate-to-severe dermatitis, especially with a history of staphylococcal infection. Oral vitamin D(3) has been suggested to increase the deficient antimicrobial peptide that results from cutaneous inflammation, although studies to date are inconclusive. Topical corticosteroids and calcineurin inhibitors continue to predominate as therapy and, to date, their safety record seems good, despite the Black Box warning issued in the United States. Poor compliance may explain the failure to respond to therapy, and contact dermatitis from topical application of emollients and medications may mimic AD, erroneously suggesting recalcitrance. For patients with severe AD, administration of systemic immunosuppressants may be required; ongoing studies of newer agents, including biologics, may revolutionize therapy for individuals with severe dermatitis, providing more targeted therapy in the future.