One of the remaining and unresolved problems in allogeneic stem cell transplantation, especially following a T cell-depleted transplant as often performed in the setting of haploidentical transplantation, is the relapse of the underlying hematological malignancy. It has been demonstrated that in the last years we have made major progress in controlling infections, acute and chronic GvHD and making stem cell transplantation available to elderly patients. However, little improvement has been made to achieve better tumor control and to lower the relapse rate. Thus, novel immunotherapeutic strategies are increasingly used prior to or even following allogeneic stem cell transplantation to better control the underlying malignancy and thus, to reduce the relapse rate. These novel immunotherapeutic strategies comprise monoclonal antibodies, immunotoxins and even more effective T cell redirecting strategies like bispecific antibodies and T cells transduced with either chimeric antigen receptors (CAR) or (affinity-tuned) T cell receptors (TCR).