Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for a majority of hematologic malignancies. However, this treatment procedure can still be associated with significant treatment-related mortality and morbidity, including regimen-related toxicity, graft-versus-host disease, and opportunistic infections. Recently, the advent of molecularly targeted therapy, such as tyrosine kinase inhibitors or antibody drugs, have changed the indications and techniques employed for allogeneic HSCT. In addition, as molecular pathogenesis of a variety of hematologic malignancies has become clear, it has been suggested that mutational profiling can potentially be used for risk stratification and to inform therapeutic decisions regarding patients with hematologic malignancies. Here, we review the knowledge regarding the current status and future directions for allogeneic HSCT in these backgrounds.