Hematopoietic stem cell transplantation aims to restore ablated myelopoiesis caused by intensive chemoradiotherapy. A minimum quantity of progenitor cells must be administered to the patients for adequate engraftment to occur (that is, to cover demanding daily needs of erythrocytes, neutrophils, and platelets). This gives the idea that the higher the quantity of progenitor cells infused to the patients, the better the results after the transplant. However, after reviewing our own data and data from other groups, it appears that the specific clinical effect of the amount of progenitor cells may depend on several factors: (1) the type of transplants, autologous or allogeneic; (2) the source of progenitor cells, either from umbilical cord, from bone marrow, or from peripheral blood; (3) the presence and the quantity of accessory cells, not only T cells, but also dendritic cells (DC1 and DC2) and mesenchymal cells; (4) the degree of human leukocyte antigen (HLA) compatibility; and (5) the underlying disease and the phase of the disease.