Proton NMR experiments on duplex DNA allow the determination of nuclear Overhauser effects (NOEs) and scalar coupling constants between nearby protons of nucleobase and sugar moieties. The original strategies rely on the use of NOE contacts between nonexchangeable protons in a regular B‐form duplex. In this chapter, we review approaches to and challenges of NMR studies of DNA beyond double‐stranded structures. NMR methods include simple resonance assignment for determining topology, typically followed by sequential assignment and high‐resolution structure determination. The low proton density of nucleic acids allows for quick recognition and identification of hydrogen bonds, which enables evaluation of folding and offers restraints for defining alignments of base pairs. Complete structure determination requires assignment of the sugar–phosphate backbone. Conventionally, the structure determination process is based on the interpretation of throughspace magnetization transfer between protons, which is mediated through carbon, nitrogen and phosphorus atoms. The power and limitations of NOE‐derived information lie in the fact that the NOE is a function of many factors, including motion, relative orientation, and mutual effects, in addition to the internuclear distance of a pair of protons. The scalar coupling constants are weighted averages over all the conformations that DNA can adopt. This, in general, limits a conversion of NOE and coupling constant information into a single structure of a duplex DNA in solution.