Current research has revealed that the influence of RNA molecules on gene expression reaches beyond the realm of protein synthesis back into the nucleus, where it not only dictates the transcriptional activity of genes, but also shapes the chromatin architecture of extensive regions of DNA. Non-coding RNA, in the context of this review, refers to transcripts expressed and processed in the nucleus much like any protein coding gene, but lacking an open reading frame and often transcribed antisense to bona fide protein coding genes. In mammals, these types of transcripts are highly coincident with allele-specific silencing of imprinted genes and have a proven role in dosage compensation via X-inactivation. The biochemistry of how non-coding RNAs regulate transcription is the subject of intense research in both prokaryotic and eukaryotic models. Mechanisms such as RNA interference may have deep phylogenetic roots, but their relevance to imprinting and X-inactivation in mammals has not been proven. The remarkable diversity of non-coding transcription associated with parent-of-origin directed gene silencing hints at an equally diverse assortment of mechanisms.