**Abstract**

In this chapter the accumulated evidence that supports the role of hyperbaric oxygen therapy (HBOT) in improving the process of hematopoietic stem/ progenitor cell (HSPC) homing, engraftment, and immune-reconstitution will be reviewed. The underlying mechanism by which HBO modulates erythropoietin (EPO)/EPOR signaling to improve HSPC homing and engraftment will be described. Also the pre-clinical evidence and pilot clinical trial evidence that supports HBO role in improving HSPC homing and engraftment will be examined. Current and future clinical trial studies that stem from this concept will be detailed. Finally, areas that need future investigations to optimally utilize HBO in the field of HSPC transplantation will be described.

**Keywords:** hyperbaric oxygen therapy (HBOT), hematopoietic stem/progenitor cell (HSPC), homing and engraftment, hematopoietic stem/progenitor cell transplantation, pilot clinical trials, phase II clinical trials
