Several solution NMR experiments have become indispensable in academia and industry for studying protein–ligand interactions. In general, solution NMR is superior to other physicochemical methods in terms of its spatial resolution and non-necessity of protein modifications. The applications of solution NMR are loosely classified into two categories: “ligand-based” approach and “protein-based” approach. Many unique experiments have been developed based on the ligand-based approach, including STD, WaterLOGSY, 19F-NMR with R2 filter, DIRECTION, INPHARMA, ILOE, and trNOE. These experiments frequently comprise the important steps of the drug discovery process, including ligand screening, fragment-based drug discovery (FBDD), pharmacophore mapping, and molecular design. This review provides a practicable classification of these experiments to aid the selection of a suitable experiment depending on the purpose. In contrast to the ligand-based approach, the experiments based on the protein-based approach are rather limited, with the 1H-15N-HSQC-based NMR titration experiment and its variants being preferentially used. This review also discusses several practical aspects of the NMR titration experiment, including data analysis and sample handling.