Since various ‘NKT’ cell populations were described over 20 years ago in man and model organisms, thoughts have turned to exploiting them in treatment of disease.  Much encouraging model data and preclinical human progress supported the diagnostic and therapeutic potential of NKT cells in general and iNKT cells in particular.  For example, NKT IFNg production stratifies for survival of cancer patients.  Unlike other CD1d-restricted T cells, iNKT can be uniformly and highly specifically manipulated with certain lipids and antibodies ex vivo and in vivo.  Safety studies showed iNKT-based approaches are well-tolerated.  More recent clinical trials worldwide have shown clear anti-tumor potential for iNKT-based treatments.  Such approaches maybe optimized by genetic modification &/or combination with complementary therapies.  Other diseases where iNKT may have positive impact will also be summarized, along with some notes of caution.