The chapter addresses the current methodologies for RNA investigation by liquid‐state NMR spectroscopy. The production of milligram amounts of isotopically labeled RNA remains crucial for the success of NMR‐based studies of the structure–function relationship. The current technology for the preparation and purification of uniformly and segmentally isotopically labeled RNA is reviewed. An overview of essential spectroscopic strategies for NMR studies of RNA is presented. The topics covered include experiments for RNA resonance assignments, the collection of distance, dihedral angle, and orientational restraints, as well as procedures for reliable structure calculations and validation. Critical steps in RNA investigations by NMR are demonstrated by protocols and examples, along with practical advice for troubleshooting.