The article discusses the role of long noncoding RNAs (lncRNAs) in genome regulation. It highlights the discovery of extensive transcription of large RNA transcripts that do not code for proteins, which has provided a new perspective on the importance of RNA in gene regulation. The authors review genome-scale strategies for discovering and characterizing lncRNAs, emphasizing their formation of extensive networks of ribonucleoprotein (RNP) complexes with chromatin regulators. They also discuss the emerging theme that lncRNAs function as modular scaffolds to specify higher-order organization in RNP complexes and chromatin states. The article further explores the functional roles of lncRNAs in various cellular processes and diseases, including embryonic stem cell pluripotency, cell-cycle regulation, and cancer. It reviews technological approaches for genome-wide discovery and characterization of lncRNAs, and evaluates studies indicating important roles for lncRNAs in disease etiology. The authors conclude by discussing the global RNA-chromatin network and the potential for lncRNAs to serve as decoys, scaffolds, and guides in gene regulation.The article discusses the role of long noncoding RNAs (lncRNAs) in genome regulation. It highlights the discovery of extensive transcription of large RNA transcripts that do not code for proteins, which has provided a new perspective on the importance of RNA in gene regulation. The authors review genome-scale strategies for discovering and characterizing lncRNAs, emphasizing their formation of extensive networks of ribonucleoprotein (RNP) complexes with chromatin regulators. They also discuss the emerging theme that lncRNAs function as modular scaffolds to specify higher-order organization in RNP complexes and chromatin states. The article further explores the functional roles of lncRNAs in various cellular processes and diseases, including embryonic stem cell pluripotency, cell-cycle regulation, and cancer. It reviews technological approaches for genome-wide discovery and characterization of lncRNAs, and evaluates studies indicating important roles for lncRNAs in disease etiology. The authors conclude by discussing the global RNA-chromatin network and the potential for lncRNAs to serve as decoys, scaffolds, and guides in gene regulation.