This review explores the features of imprinted loci that have been uncovered by genetic experiments in the mouse. Imprinted genes are expressed from one parental allele and often contain parent-specific differences in DNA methylation within genomic regions known as differentially methylated domains (DMDs). The precise erasure, establishment, and propagation of methylation on the alleles of imprinted genes during development suggest that parental differences in methylation at DMD sequences are a fundamental distinguishing feature of imprinted loci. Furthermore, targeted mutations of many DMDs have shown that they are essential for the imprinting of single genes or large gene clusters. An essential role of DNA methylation in genomic imprinting is also shown by studies of methyltransferase-deficient embryos. Many of the DMDs known to be required for imprinting contain imprinted promoters, tandem repeats, and CpG-rich regions that may be important for regulating parent-specific gene expression.