Hematopoietic cell transplantation using disparate related or volunteer unrelated donors is associated with substantial allogeneic complications. DNA technology, enabling discrimination at the allelic level for class I and II human leukocyte antigens, has helped us better understand these complications. Recent information demonstrates that better donor matching, more intensive conditioning regimens, and improved prevention and management of allogeneic complications can improve outcome. Many diseases that have been previously treated with related matched hematopoietic cell transplantation are now undergoing mismatched related and volunteer unrelated donor hematopoietic cell transplantation. Outcome, especially for patients with suitable donors and satisfactory prognostic features, compares favorably with outcome from matched related donors, though further improvement is required.