The use of a human leukocyte antigen compatible unrelated donor is a valid option for candidates of allogeneic transplantation without a family member match. The current access to large registries including almost 8 million human leukocyte antigen typed volunteers makes this type of transplants feasible. Grafts from unrelated donors provide long-term disease-free survival for a remarkable proportion of patients with the results depending on patient's age, disease, disease stage, degree of human leukocyte antigen matching with the donor, and progenitor cell dose infused. Prevention and treatment of graft-versus-host disease and opportunistic infections remain a challenge. With more precise donor selection by means of high-resolution DNA techniques, the results of transplants from unrelated donors are approaching to those achieved with human leukocyte antigen identical siblings. The identification of permissible mismatches and the refinement of transplantation techniques will improve the results of this type of transplant in the near future.