High-resolution NMR spectroscopy provides a large variety of experimental approaches that target on the characterization of samples at atomic resolution. This capacity is of special interest when it comes to the investigation of biological molecules to obtain insights into their inherent structural and dynamical features and ultimately, their functionality. Consequently, it emerged as one of the leading methodologies in structural biology, life science, and biophysics. The correlation of different nuclear spins and an increase in the number of dimensions sort out the problem of overlapping resonance signals which is commonly present in one-dimensional NMR spectroscopy. While three- and even higher dimensional NMR experiments are usually acquired to unambiguously achieve resonance assignment, two-dimensional NMR spectra such as heteronuclear 1H-15N and 1H-13C HSQC approaches can report on subtle conformational and dynamical changes and are thus an integral part in the large variety of sophisticated experiments. This chapter aims to show the strength of NMR spectroscopy especially when it is performed in multi dimensions on biomolecules that vary in type and composition as well as in the environment in which they are existing. Thus, the importance of modern NMR techniques in the context of in vivo as well as integrative approaches is discussed. Another pillar of this Chapter comprises case studies. Here, also non-standard (“exotic”) applications of NMR correlating nuclei are highlighted. The diversity of experimental possibilities multi-dimensional high-resolution NMR spectroscopy offers suggest a continuous expansion of applications on biomolecules. This dynamic development is strongly promoted by the permanent increase in instrumental sensitivity and performance.