Uniparental disomy (UPD), the inheritance of both homologues of a chromosome pair from only one parent, has meanwhile been described for the majority of human chromosomes. In many instances there is no associated phenotype, indicating that these chromosomes do not harbour imprinted genes. UPD of other chromosomes give rise to distinct phenotypes: the most prominent entities are Prader-Willi and Angelman syndromes which are associated with maternal UPD or paternal UPD of chromosome 15. The molecular basis for the clinical features of UPDs are specific human genes that are only monoallelically active, depending on whether they are located on the paternal or maternal chromosome (“genomic imprinting”). UPD leads to an imbalanced expression of these imprinted genes and cause abnormal development. The frequencies of UPDs in the general population are unknown, but some clinical and cytogenetic findings are predisposing for UPD identification: (a) specific clinical pictures (Prader-Willi, Angelman, Silver-Russell, Beckwith Wiedemann syndrome, transient neonatal Diabetis mellitus) indicate UPD of the respective chromosome; (b) carriers of Robertsonian translocations are at an increased risk to produce UPD offspring; (c) carriers of small supernumerary marker chromosomes and isochromosomes can show a UPD. UPD can be detected in patients with chromosomal aberrations as well as in carriers of normal chromosomal complements. In addition, a UPD can affect a whole chromosome but can also be restricted to a segment (segmental UPD). In this review the current knowledge on the role of UPDs in human diseases and a correlation with the mode of UPD formation will be presented.