Langerhans cells (LCs) have long been considered to be the major sensitizing cells in the skin by initiating productive immunity in naive resting T cells. This picture has changed over the past decade. We now know (i) that the skin also harbors other types of dendritic antigen-presenting cells and (ii) that the genetically driven removal of the LC population results in increased T-cell immunity against haptens and infectious agents. It is not clear at present whether the situation in genetically modified mice is in any way indicative of the actual in vivo function of LCs. Exciting and challenging years lie ahead of the LC research community.