iNKT cells are known for their ability to promote seemingly contrasting tolerogenic and pro-inflammatory immunological outcomes.  Understanding the mechanisms by which they mediate these opposing effects remains a central challenge in our field.  Our prior studies have demonstrated that human iNKT cells interact efficiently with monocytic cells, and thereby influence not only the differentiation state of the APC and its subsequent interactions with other lymphocytes, but also affect the physiology of the local tissue environment.  Here, I will extend these results to an in vivo model system showing the pronounced effects of human iNKT cells on hematopoiesis, and will discuss how the hematopoietic functions of iNKT cells may relate to graft-vs-host disease and control of leukemias.