Autologous hematopoietic stem cell transplantation has proved to be an effective treatment for certain hematologic malignancies. However, relapse rates are high during the first year after transplantation. These relapses are attributed to the failure of high-dose chemotherapy to eradicate minimal residual malignant disease. In allogeneic hematopoietic stem cell transplantation, the higher antitumor effects observed compared with those in autologous hematopoietic stem cell transplantation are based on the immunologically mediated graft-vs-tumor effect. Therefore, a better understanding of the mechanisms involved in immune reconstitution after hematopoietic stem cell transplantation may clarify the importance of various components of the recovery of the immune system as they pertain to eradication of residual tumor, as well as uncover possible interventions directed at maximizing this effect. This review focuses on immune reconstitution after autologous hematopoietic stem cell transplantation. Autologous hematopoietic stem cell transplantation is not affected by graft-vs-host disease or immunosuppressive therapy after transplantation to control graft-vs-host disease, providing a direct insight into the mechanisms involved in immune reconstitution after engraftment.