Current cytotoxic treatment protocols induce complete remission (CR) in most acute leukemia patients [both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)], in some patients with chronic lymphocytic leukemia (CLL), and in most non-Hodgkin’s lymphoma (NHL) and chronic myeloid leukemia (CML) patients. Introduction of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) in treatment protocols has further increased the remission rates in ALL, AML, CML, and NHL. Nevertheless, many of these patients ultimately relapse. Apparently, the treatment protocols are not capable of killing all clonogenic malignant cells in these patients, even though they reached CR according to cytomorphological criteria. The detection limit of cytomorphological techniques is not lower than 1% to 5% of malignant cells, implying that these techniques can provide only superficial information 46about the effectiveness of the treatment. More sensitive techniques are required for the detection of low frequencies of malignant cells during and after treatment, i.e., detection of minimal residual disease (MRD). MRD techniques should reach sensitivities of at least 10−3 (one malignant cell within thousand normal cells), but sensitivities of 10−4 to 10−6 are preferred. Such sensitivities allow “true” MRD detection and thereby evaluation of the effectiveness of the total treatment and assessment of the contribution of each treatment phase.