Reduced-intensity conditioning (RIC) regimens were initially introduced to provide allogeneic stem cell transplantation (HCT), a potentially curative procedure for myeloid malignancies, for patients who were not considered eligible for conventional myeloablative HCT either because of advanced age or excessive comorbidities. A variety of RIC regimens have been studied. The exact definition of RIC remains arbitrary and generally depends upon the perceived toxicity of a given regimen rather than the actual dose of chemotherapy or radiotherapy administered. In several published series, RIC regimens have demonstrated a reduction in non-relapse mortality (NRM), thereby accomplishing the initial goal of expanding the patient population eligible for this potentially curative procedure. Most retrospective studies performed to date have shown a decrease in NRM and an increase in relapse-related mortality with the use of RIC as opposed to conventional myeloablative HCT in myeloid malignancies. This appears to be particularly true for patients who are in relapse at the time of HCT. In contrast, patients who are in remission at time of HCT appear to have a reduction in NRM without a subsequent increase in relapse-related mortality. There is interest in applying RIC to younger patients and to patients with fewer comorbidities as they may have a reduction in NRM without a concomitant increase in relapse. Prospective multicenter studies are needed to define the optimal conditioning regimen, which is likely dependent upon a variety of disease-specific and patient-specific factors.