The t(9;22) translocation, which results in a fusion protein with abnormal tyrosine-kinase activity, plays a central role in the pathogenesis of chronic myeloid leukemia. The selective inhibition of this chimeric protein with imatinib-mesylate is an efficient therapeutic option, haematologic and cytogenetic responses can be achieved in most of the patients. The primary goal of monitoring the disease is to assess the efficiency of the therapy, to highlight those patients, whose survival may be improved by modifying treatment. Three methods are widely used for the genetic monitoring of chronic myeloid leukemia. With karyotyping, the proliferating bone marrow cells can be evaluated. The use of fluorescent in situ hybridization makes the cytogenetic analysis of each cell within the sample possible. Real-time quantitative polymerase chain reaction is capable of quantifying residual leukemia far below the sensitivity of cytogenetics. The results of these three methods have different biological meanings, thus, for the interpretation of the results, the knowledge of the characteristics, the benefits and the draw-backs of the methods is required. The present study shows the most important characteristics of these methods based on the literature and data acquired from 1165 samples of 197 patients detected by the authors.