Three systems of monoallelic gene expression in mammals are known, namely, X-chromosome inactivation, imprinting, and allelic exclusion. In all three systems, monoallelic expression is regulated epigenetically and is frequently directed by long non-coding RNAs (ncRNAs). This review briefs all three systems of monoallelic gene expression in mammals focusing on chromatin modifications, spatial chromosome organization in the nucleus, and the functioning of ncRNAs.