Due to years of sophisticated research on T cell function, many dermatologists have viewed atopic dermatitis (AD) largely as an inflammatory disorder of TH1/TH2 imbalance. Hence, therapy has largely consisted of topical immunomodulators and/or steroids. The imposition of "black box" warnings about the potential toxicity associated with prolonged use of the immunosuppressive drugs, tacrolimus 0.1% or 0.3% ointment (Protopic((R)), Astellas Pharma U.S., Inc., Deerfield, IL) and pimecrolimus 1% cream (Elidel((R)), Novartis, Basel, Switzerland), as well as legitimate concerns about the adverse side effects of potent topical steroids, has stimulated a search for alternate forms of therapy. Recent genetic studies point to the primary role of a defective barrier to water loss and microbial invasion in the provocation of AD, creating a rationale for 'barrier repair' therapy. This approach utilizes topical applications of specific combination of the three (3) epidermal lipids that comprise the epidermal permeability barrier in a ratio (ceramide-dominant) that corrects the biochemical abnormality in AD.1,2 We review here both recent concerns about the topical immunomodulators, as well as the rationale for barrier repair therapy.