We discuss and demonstrate the potential of HSQC-TOCSY and HSQC-NOESY experiments to offer solutions for overlap problems in COSY and NOESY spectra, leading to improved signals that can be unambiguously assigned to individual carbons. Direct comparison of experimental (1)H and (13)C chemical shielding with density functional theory (DFT)-calculated values are uninformative; in contrast, the relative differences in experimental shielding between pairs of molecules correlates well with the relative differences in DFT-GIAO shielding for the computed lowest energy conformers. A detailed application of both experimental and theoretical techniques is illustrated for slowly exchanging conformers of an erythronolide A derivative, which demonstrates that structure determination can strongly benefit from the interplay between experiment and theory.