Since the fundamental discovery in 1956 that normal human cell contain 46 chromosomes, human cytogenetics has been transformed by technological advance that have greatly improved resolution and sensibility, first with the introduction of banding and high resolution technologies and, latter, with the fluorescent in situ hybridization (FISH). These latest technique allow to detect extremely subtle alterations in chromosome constitution and had made possible to evaluate the karyotype of non-dividing cells. The latest transformation of cytogenetics came with the technique of comparative genome hybridization which allows genome-wide screens for the loss or gain of chromosomal material in test samples relative to normal controls. Nevertheless, only the conventional cytogenetics techniques are able to detect balanced chromosomals rearrangements particularly in phenotypically abnormal patients in whom candidate genes may be disrupted or functionally altered. Thus, Cytogenetics will still play a central role in our understanding of the molecular basis of human hereditary diseases.