Normal mammalian development requires a maternal and paternal contribution, which is attributed to imprinted genes, or genes that are expressed from a single parental allele. Approximately 100 imprinted genes have been reported in mammals thus far. Imprinted genes are controlled by cis-acting regulatory elements, termed imprinting control regions (ICRs), which have parental-specific epigenetic modifications, including DNA methylation. ICRs are methylated by de novo DNA methyltransferases during germline development; these parental-specific modifications must be maintained following fertilization when the genome is extensively reprogrammed. Many imprinted genes reside in ∼1-megabase clusters, with two major mechanisms of imprinting regulation currently recognized, CTCF-dependent insulators and long noncoding RNAs. Unclustered imprinted genes are generally regulated by germline-derived differential promoter methylation. Here, we describe the identification and functions of imprinted genes, cis-acting control sequences, trans-acting factors, and imprinting mechanisms in clusters. Finally, we define questions that require more extensive research.