The epidermis protects human subjects from exogenous stressors and helps to maintain internal fluid and electrolyte homeostasis. Filaggrin is a crucial epidermal protein that is important for the formation of the corneocyte, as well as the generation of its intracellular metabolites, which contribute to stratum corneum hydration and pH. The levels of filaggrin and its degradation products are influenced not only by the filaggrin genotype but also by inflammation and exogenous stressors. Pertinently, filaggrin deficiency is observed in patients with atopic dermatitis regardless of filaggrin mutation status, suggesting that the absence of filaggrin is a key factor in the pathogenesis of this skin condition. In this article we review the various causes of low filaggrin levels, centralizing the functional and morphologic role of a deficiency in filaggrin, its metabolites, or both in the etiopathogenesis of atopic dermatitis.