Bone marrow transplantation is an important therapeutic modality in the treatment of hematological malignancies and other hematological diseases. It is typically marred by complications like graft-versus-host disease, engraftment failure of donor cells, and recurrence of the original disease. Epigenetic modifications like DNA methylation, histone modification, and noncoding RNAs play a pivotal role in regulating gene expression and cellular function. Current advances in epigenetics studies have heightened the expectation that they have the potential to enhance the efficacy of transplantation by regulating immune response, improving donor cell engraftment, and manipulating the tumor microenvironment. The current chapter discusses the implication of epigenetic modification for the solution of the issues in bone marrow transplantation, with a special focus on how they can impact graft-versus-host disease, hematopoietic reconstitution, and relapse of cancer. By integrating epigenetic therapies and biomarkers into transplant regimens, the possibility exists to improve patient outcomes and advance personalized medicine in oncology.