DNA is a major target for metal‐based anticancer drugs, including platinum diamine complexes, which are widely used in the clinic and organometallic complexes. The modes of binding include coordination to bases, groove binding, intercalative and insertion binding, and dual‐mode coordination and intercalation. Coordinative complexes, such as cisplatin and its analogs, form direct coordination bonds between the metal center and DNA bases. Groove‐binders, such as [Fe 2L 3] 4+ cylinders and multinuclear platinum complexes, which have no leaving groups, bind to the walls and floor of DNA major or minor grooves by van der Waals interactions. For coordinatively saturated kinetically inert metal complexes (e.g., square‐planar Pt(II) complexes) and octahedral complexes with aromatic ligands, DNA intercalation or insertion is observed. Coordination complexes with σ‐bonded aromatic side‐arms as intercalators or organometallic complexes with π‐bonded arene as intercalators are dual‐function complexes, in which the intercalation into DNA involves the aromatic side‐arms or arene ligands, while the metal coordinates directly to a DNA base. NMR is powerful for identifying metal‐binding sites on DNA, for elucidating the nature of metal‐induced structural changes (e.g., bending, loss of base pairing, base extrusion, and intercalation), as well as the kinetics and mechanism of their formation. In this chapter, we describe the use of NMR methods for such studies, including protocols for the determination of coordination sites, detection of DNA intercalation, insertion, and groove‐binding interactions. Ways of overcoming particular problems associated with the interpretation of complex nuclear Overhauser effect spectroscopy (NOESY) spectra arising from the binding of bulky intercalators are discussed.