Langerhans cells (LCs) are a specialized subset of dendritic cells (DCs) that populate the epidermal layer of the skin. Langerin is a lectin that serves as a valuable marker for LCs in mice and humans. In recent years, new mouse models have led to the identification of other langerin⁺ DC subsets that are not present in the epidermis, including a subset of DCs that is found in most non-lymphoid tissues. In this Review we describe new developments in the understanding of the biology of LCs and other langerin⁺ DCs and discuss the challenges that remain in identifying the role of different DC subsets in tissue immunity.