Graft versus host disease (GvHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT) and is the main cause of transplant-related mortality (TRM). In addition to visceral organ involvement, concomitant myelosuppression has been repeatedly described and the extent of cytopenia has been introduced into GvHD scoring systems. Both hematopoietic cells and cells that form the hematopoietic stem and progenitor cell (HSPC) niche have been identified as targets of GvHD. Although several contributing factors have been previously described, the pathophysiology of GvHD-mediated myelosuppression remains largely unclear and to date, no specific therapeutic interventions have achieved routine clinical application. This review focuses on the bone marrow as a target of GvHD, the factors that contribute to myelosuppression, and the possible therapeutic approaches. Stem Cells 2014