Invariant natural killer T (iNKT) cells are a small but powerful subset of regulatory T cells involved in the modulation of a variety of normal and pathological immune responses. In contrast to conventional or other types of regulatory T cells, they are activated by glycolipid and phospholipid ligands that are presented to them by the non-polymorphic, major histocompatibility complex class I-like molecule CD1d. The in-depth understanding of their function has resulted in successful, iNKT cell-centred experimental therapeutic interventions including prevention of graft-versus-host disease and anti-leukaemia effects. Extending these successes into the clinical arena will require better understanding of their contribution to the pathogenesis of human, including haematological, diseases.