Patients with atopic dermatitis exhibit an increased susceptibility to cutaneous infections, especially to pathological colonization with superantigen-secreting Staphylococcus aureus. Recent attention has been focused on antimicrobial peptides, especially on cathelicidin and human beta-defensin-2, which are under-expressed in atopic skin. Antimicrobial lipids from the stratum corneum are also major contributors to cutaneous antimicrobial defense. Current aspects of biochemistry and function of antimicrobial lipids in atopic dermatitis are reviewed in detail. The major classes of stratum corneum lipids with antimicrobial activity are free fatty acids, glucosylceramides, and free sphingosines. Diminished levels of free sphingosines in the stratum corneum have recently been detected in atopic dermatitis and have been associated with the pathological colonization of atopic skin with Staphylococcus aureus. The superantigen staphylococcal enterotoxin B has been shown to reduce the suppressive effect of regulatory T cells on T-cell proliferation, thus augmenting T-cell activation in patients with atopic dermatitis. The killing of superantigen-secreting bacterial strains with topically applied antimicrobial lipids offers new antiseptic and immunomodulatory options for the treatment and secondary prevention of atopic dermatitis.