The idea that abnormality could be due to a correct amount of chromosome material overall, but with unequal parental contributions, seemed most remarkable in 1980 when Engel [1] first made the suggestion and coined the expression “uniparental disomy” (or UPD). The idea was supported by the high rate of aneuploidies in spontaneous abortions. A decade later, the concept had progressed from esoteric theory to an important and illuminating practical­ity [1]. The two disorders which, par excellence, exem­plify the concept of qualitative imbalance are Prader-Willi syndrome (PWS) and Angelman syndrome (AS), which were first associated with maternal and paternal UPD 15, respectively [2,3]. From that time, UPD was more than a theoretical concept, and the interest in it and its conse­quences increased rapidly. So far, several hundred cases of UPD have been reported. Maternal UPD 15 still repre­sents the majority of instances. However, more and more cases of UPD of other chromosomes have recently been published, and have been implicated as causative of phe­notypic abnormality. Uniparental disomy causes abnormal­ity when a chromosome segment is subject to genomic imprinting [4]. A thorough investigation of the literature on UPD has been published by Kotzot [5]. In this article, it will be attempted to discuss the implications of UPD, mainly in prenatal diagnosis.