This article reviews the biology of hematopoietic stem cells (HSCs), the clinical efficacy of hematopoietic stem cell transplantation (HSCT), transplantation procedures, and potential complications. HSCs are undifferentiated cells capable of indefinite self-renewal and generating a functional progeny of mature blood lineages. HSCT is used to treat various hematological malignancies, immune deficiencies, and genetic disorders. The selection of HSC source depends on donor availability and transplantation indications, with autologous, syngeneic, and allogeneic options available. Bone marrow, peripheral blood, and umbilical cord blood are common sources for HSCs. The conditioning regimen used before transplantation varies, with less-intensive regimens increasing the use of allogeneic HSCT in older patients. The GvHD and GvT effects are crucial for the success of HSCT, with GvHD being a major cause of early mortality. The article also discusses the hematopoietic cell transplantation comorbidity index (HCT-CI) for risk assessment and the management of complications such as infections and GvHD. Despite advancements, HSCT remains associated with significant morbidity and mortality, particularly in the early post-transplant period.This article reviews the biology of hematopoietic stem cells (HSCs), the clinical efficacy of hematopoietic stem cell transplantation (HSCT), transplantation procedures, and potential complications. HSCs are undifferentiated cells capable of indefinite self-renewal and generating a functional progeny of mature blood lineages. HSCT is used to treat various hematological malignancies, immune deficiencies, and genetic disorders. The selection of HSC source depends on donor availability and transplantation indications, with autologous, syngeneic, and allogeneic options available. Bone marrow, peripheral blood, and umbilical cord blood are common sources for HSCs. The conditioning regimen used before transplantation varies, with less-intensive regimens increasing the use of allogeneic HSCT in older patients. The GvHD and GvT effects are crucial for the success of HSCT, with GvHD being a major cause of early mortality. The article also discusses the hematopoietic cell transplantation comorbidity index (HCT-CI) for risk assessment and the management of complications such as infections and GvHD. Despite advancements, HSCT remains associated with significant morbidity and mortality, particularly in the early post-transplant period.