A “hit” is a molecule identified from a screening technique (HTS, FBDD, etc) as having a desirable effect (i.e., decreased cellular growth, high affinity score) on a target [365,366]. However, the question of whether the activity is related to actual binding to the target, or to interference with one of the components of the assay readout mechanism, is uncertain. Thus, a validation step is required. Hit-validation is therefore the process of confirming, or validating, that the molecule(s) identified previously have on target activity and selectivity [367,368]. One of the highest-impacts of NMR on drug discovery is the use as a hit-validation tool. Though the hit-validation or confirmation of drugs is mostly limited to the solution state [369], this aspect of NMR truly is a “gold standard” technique in drug discovery.