The skin is the largest organ in the human body. It acts not only as an important structural barrier against injury but also as a peripheral arm of the immune system. Elucidating the characteristics of this latter function has taken on renewed importance in recent years. Exposure to chemicals in everyday life has increased exponentially over the past decades. This has been accompanied by an increased incidence of contact hypersensitivity (CHS), a dendritic cell-dependent, T cell-derived, cytokine-mediated skin inflammation. Cytokines derived from Langerhans cells (i.e., interleukin-12 [IL-12]) and from T cell (i.e., interferon-gamma [IFN-gamma], IL-4, and IL-10) play a pivotal role in the induction and initiation of CHS. Developments in immunology and molecular biology have improved our understanding of the molecular mechanisms underlying this immune response. However, the conflicting opinions that continue to characterize discussions of CHS supply clear testimony that our knowledge is as yet incomplete.