NMR (nuclear magnetic resonance) spectroscopy is a powerful technique to study biomolecular interactions as it provides information at atomic resolution. In this chapter we present a short overview on how NMR spectroscopy can be applied to probe ligand-binding processes. Out of the limit of fast chemical exchange regime the positions (or frequency resonances) of the peaks are no longer suitable to obtain binding parameters in terms of chemical shifts. We present in more detail a model recently published for analyzing NMR titration curves based on peak intensities which takes into account chemical exchange effects on peak intensities. The dissociation constant is determined by fitting data with or without influence of chemical exchange. The thermodynamic parameters can be extracted from dissociation constants which can be easily determined by fitting NMR titration binding curve. Finally, we provide a short protocol for data acquisition, processing to obtain peak resonance frequencies and their respective intensities, and obtention of dissociation constant and parameters linked to chemical exchange.