Evidence from animal models has shown that the transfer of regulatory T cells or tolerogenic dendritic cells can prevent or cure transplant rejection or re-establish self-tolerance in autoimmune disease. The potential of these tolerogenic cells for the treatment of T-cell-mediated diseases in humans has gained momentum in recent years. Here, Nature Reviews Immunology asks four leading researchers to provide their view on the future of cell-based tolerogenic therapy and to highlight some important issues that must be considered before this form of immunotherapy can become a reality.