Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. Unfortunately, it carries a high risk of complications and toxicities related to the intensive preparative regimen which is traditionally used for pre-transplant myeloablation and the graft versus host disease, which may be life threatening. Thus allogeneic stem cell transplantation has been used only for younger patients with a good performance status, excluding many other potential candidates due to advanced age or comorbid conditions. Using reduced intensity preparative regimens for allogeneic stem cell transplantation (non-myeloablative stem cell transplantation (NST)) researchers attempted to overcome these barriers in patients' selection and tried to make hematopoietic stem cell (HSC) transplantation a safer procedure. The well-described graft versus malignancy effect would be the most curative element in this treatment. After more than 5 years of cumulative clinical experience, we know that NST is a feasible treatment option for patients with suboptimal performance status and is mostly effective in slow proliferating malignancies, which gives time for a graft versus malignancy effect to take place. Additionally achievement of stable donor cell engraftment with NSTs provides a platform for adoptive immune cell treatments and is promising for extended indications of stem cell transplantation in the future.