This session will provide an overview of malignant and nonmalignant diseases treated by unrelated hematopoietic cell transplantation (HCT) including the leukemias, lymphomas, marrow failure syndromes, inherited immunodeficiencies, inborn errors of metabolism and hemoglobinopathies. The molecular basis for these disorders will be reviewed including how they may be diagnosed based on clinical and laboratory studies. The rationale for choosing HCT as the therapy will be explored including which clinical factors favor a better prognosis for the patient.