Dendritic cells (DC) are professional antigen presenting cells and crucial mediators of immune defence and tolerance. Experimental evidence in vitro and in vivo has shown that tolerogenic DCs (tDCs) contribute to prevention of autoimmunity and allergic reactions but might also worsen the course of cancer and certain infectious diseases. The development of in vitro protocols for the generation of human tDCs has greatly improved the knowledge of basic principles for tolerance induction by tDCs and fosters approaches for the therapeutic manipulation of tDCs in conditions such as severe autoimmunity, allergy or transplantation.