Atopic dermatitis (AD) is a common, chronic inflammatory skin disease that becomes clinically apparent in the pediatric population. It is well recognized that subjects with AD have an increased susceptibility to cutaneous colonization and infection with bacteria, fungi, and viruses. The notion that subjects with AD have a cutaneous immune defect has received widespread acceptance, and several plausible explanations for this have been proposed. We will review the evidence that this susceptibility to cutaneous infection is at least in part due to a defect in the first line of defense against microbes, namely the innate immune system.