Allogeneic hematopoietic SCT is well established as a potentially curative therapy for children and adults with both malignant and nonmalignant diseases. However, myeloablative SCT is associated with significant short- and long-term complications. The goals of a reduced intensity-conditioning (RIC) regimen are to prevent graft rejection and establish stable donor-derived hematopoiesis at a level sufficient for cure of the underlying disease and, in patients with hematologic malignancy, to provide a GVL effect, while decreasing the short- and long-term complications associated with myeloablative conditioning therapy. RIC regimens have enabled SCT to be performed in children with preexisting comorbidities that preclude conventional conditioning. RIC-SCT has been most extensively studied in patients with nonmalignant disorders and for some of these, including primary immunodeficiencies and hemophagocytic lymphohistiocytosis, sufficient data now exist to support its routine use even in patients without comorbidity. Less data exist on RIC-SCT for children with hematologic malignancies and at present this should be restricted to children who are not candidates for, or have relapsed after, myeloablative SCT. Here we review available data on the use of RIC-SCT in pediatric patients, highlighting important clinical lessons and areas that require further study.