Atopic dermatitis (AD) is a common inflammatory skin disease with increasing prevalence since World War II. Recent studies have shed light on how the complex interrelation of genetic, environmental, immunologic, and pharmacologic factors contributes to the development of AD. The current review will examine the cellular and immunologic mechanisms underlying AD as well as the potential role of microbial superantigens in the pathogenesis of AD. An understanding of the relative contributions of allergens, IgE, T cells with skin homing capability, Langerhans cells, keratinocytes, eosinophils, and mast cells to the inflammatory process in AD may lead to improved treatments for this potentially debilitating disease.