One therapeutic concept in chronic myeloid leukemia (CML) assumes that a reduction of clonal genetically unstable cells also reduces the rate of secondary genetic changes and thereby postpones blast crisis. According to this concept, the degree of reduction of tumor burden should correlate with a prolongation of survival. The recent literature, in particular on controlled studies of IFN, hydroxyurea or intensive chemotherapy is reviewed and analyzed with regards to this concept. In chronic phase CML, intensity of treatment as determined by the degrees of WBC suppression, and, more recently, of cytogenetic remission, as measures of the reduction of tumor burden appear to correlate directly with survival. The superiority of a therapeutic regimen in chronic phase CML seems to primarily depend on whether its pharmacology permits a sufficiently high dosage to achieve the necessary reduction of tumor burden. The concept underlies present strategies that try to prolong survival in CML by IFN alone or in combination with intensive chemotherapy, by hydroxyurea, alone or in combination with IFN, and by high-dose chemotherapy followed by autografting.