Several studies in the early 1990s demonstrated that cyclophosphamide (Cy) combined with oral busulfan was inferior to total body irradiation (TBI) for outcomes of myeloablative transplantation. However, since the development of IV busulfan preparations, the optimal preparative regimen has been controversial. Two manuscripts published in this week's issue of Blood compare the outcomes of hematopoietic cell transplant following preparation with cyclophosphamide plus total body irradiation (Cy-TBI) versus IV busulfan (Bu-Cy) and confirm superior results with Bu-Cy, including improved leukemia-free survival and reduced non-relapse mortality, suggesting that this regimen should be the standard of care.