Genomic imprinting is epigenetic phenomenon where gene activity is regulated according to parent of origin. Imprinted gene is expressed from only one allele, while the allele inherited from the other parent is silenced (inactivated). This monoallelic expression is in contrast to classical Mendelian inheritance where both alleles contribute to phenotype equally. Genomic imprinting is maintained by epigenetic modifications that occur during gametogenesis and early embryonic developement and include chemical modifications to the DNA, with no alterations in the base sequence. Three main and interconnected epigenetic mechanisms are: methylation of CpG dinucleotides, covalent modifications of histones, and RNA interference. Imprinted genes are clustered into domains, rich in CpG islands. The first and best described human genetic disorders associated with genomic imprinting are Prader-Willi syndrome and Angelman syndrome. Each of these syndromes has its characteristic phenotype with neurodevelopmental abnormalities and behavioral and functional difficulties. Although clinically two distinct disorders, Prader-Willi and Angelman syndromes are caused by the deletion of the same region on the proximal long arm of chromosome 15 (q11-q13). The difference is the parental origin of the affected chromosome: functional loss of paternally expressed genes will cause Prader-Willi syndrome, and loss of maternal UBE3A expression in the brain will lead to Angelman syndrome. Imprinted expression of the genes in 15q11-q13 region is controled by PWS/AS imprinting center (IC), comprising two functional regions: the PWS-SRO and the AS-SRO. The maternal state is associated with methylation of the PWS-SRO and unmethylated AS-SRO, while the paternal state is characterized with lack of methylation of the PWS-SRO and methylated AS-SRO.