Contact hypersensitivity (CHS) is a Langerhans cell (LC)-dependent, T cell-mediated cutaneous immune response. CHS reflects a culmination of LC activities in vivo: uptake of epicutaneous antigens, migration into lymph nodes, and presentation of antigens to naïve T cells. Although studies have suggested involvement of the cytokine network in LC migration and CHS initiation, the in vivo function of individual cytokines remains largely unknown. Gene targeting technology has made it possible to study in vivo functions of cytokines through gene-targeted knockout (KO) mice deficient in a given cytokine or its receptor. A variety of cytokine knockouts have been used to assign biological functions to specific cytokines in CHS. These studies have contributed significantly to our understanding of molecular mechanisms underlying CHS.