The existence of neoplastic cells with low or no sensibility to antiblastic drugs represents the most important cause of relapse in hematological malignancies. The amount of leukemic cells that remains after antiblastic chemotherapy represents the minimal residual disease. These cells can re-expand at any moment, even after months or years, causing short-term or long-term relapse. The minimal residual disease is not always detectable with morphological examination. The recent utilization of techniques such as cell culture by stimulation with growth factors and genetic amplification have made it possible to reach resolutions of more than 1-10(5) cells. The therapeutic strategies for total eradication of residual neoplastic cells are currently under investigation. The combined use of biological responder modifiers with chemotherapy or the use of immunotherapy with Interleukin-2 or LAK cells has provided one possible solution to this problem.