In addition to the advantages provided by NMR, it is often used with complementary methods such as X-ray crystallography, HPLC, and mass spectrometry [69]. An example of this is found in work by Wyss et al. [36], where they combined X-ray crystallography with NMR fragment-based screening to create the first inhibitor candidate for BACE-1 in Alzheimer’s disease. BACE-1 is a membrane-anchored aspartic acid protease and is responsible for the production of amyloid beta peptides in neurons related to the progression of Alzheimer’s disease [36,70]. Using NMR fragment-based screening, Wyss et al. identified isothiourea as binding to BACE-1 and confirmed this observation with the X-ray crystal structure of the complex of a ligand-efficient isothiourea fragment. Information obtained from these experiments aided in design optimization, resulting in the selection of iminopyrimidinones as BACE-1 inhibitors [36]. This is a perfect example of using different complementary methods to maximize scientific outcome. However, in order to be efficient, one must know the advantages and disadvantages of each method. One of the major issues regarding NMR is the effective size restriction when measuring targets such as proteins above 40kDa. Recent progress has extended this mass limit; an example of this is the resolved structure of chaperone SecB in complex with unstructured proPhoA (PDB ID 5JTL) with a total mass of 119kDa using NMR [71]. In this review, we present practical guideline to use NMR techniques in drug design studies and provide examples of the successful use of NMR in drug-design.