CD1d-restricted Natural Killer T cells (NKT cells), a novel lymphocyte lineage, are considered to play an intermediary role bridging innate and acquired immunity. This review discusses the characteristics of NKT cells and their biological significance in the immune system, and summarizes their in vivo functions observed in a number of pathological settings, including infectious diseases, cancer, autoimmunity, and transplantation. Further, we discuss recent data that have generated considerable interest in utilizing NKT cells as targets of new therapeutic interventions in various human diseases.