Dendritic leucocytes are professional antigen-presenting cells with inherent tolerogenic properties and are regarded as critical regulators of innate and adaptive immunity. Modification of dendritic cells (DCs) in the laboratory can enhance and stabilise their tolerogenic properties. Numerous reports suggest that such immature, maturation-resistant or “alternatively activated” DCs can regulate autoreactive or alloreactive T-cell responses and promote or restore antigen-specific tolerance in experimental animal models. The first clinical testing of tolerogenic DCs in human autoimmune disease, including rheumatoid arthritis, is imminent. Herein the properties of tolerogenic DCs and prospects for their testing in chronic inflammatory disease and transplantation are reviewed.