Transplant-related mortality and morbidity (both short and long term) have limited the effectiveness of SCT in children with both malignant and nonmalignant diseases. Reduced-intensity preparative regimens permit engraftment of allogeneic cells without many of the toxicities associated with standard TBI- and non-TBI-based conditioning. We review the concepts that underlie reduced-intensity transplantation (RIT) and highlight the experience of the technique in children. Although acute organ damage may be reduced after these transplants, the overall incidence of severe infections and of GvHD may be similar to that seen after standard-intensity transplantation. The relatively small numbers of children who have received RIT and the newness of the technique preclude long-term follow-up with which to monitor the incidence of associated long-term side effects and disease-free survival. Future refinements in RIT and appropriate patient selection for these procedures will hopefully extend its utility in the future.