Covalent inhibitors with highly reactive groups react nonselectively with their targets; not only may they react at the protein's active site but at other positions within the target protein and with other proteins with similar functional groups. Covalent inhibitors with less reactive groups react with specific functional groups (and hence residues) of the target. The covalent bond prevents or slows down the dissociation of the guidance system from the target protein, providing longer-lasting inhibition than a noncovalent inhibitor. The bonds formed between the covalent inhibitor and its target depend on the amino acid residue and reactive group of the target and inhibitor, respectively. While cysteine residues have been the most common targets for covalent inhibitors, serine, threonine, lysine and tyrosine residues and N-terminal amino groups are also potential reactive sites. The choice of reactive group is dictated by the nature/identity of the intended target residues. Acrylamide, cyanoacrylamide, and other α,β-unsaturated carbonyl compounds are common warheads targeting cysteine residues. Aldehydes, boronic acids, and fluorosulfates have been used as amine-reactive warheads (for either lysine residues or with N-terminal amines) in proteins. Vinyl sulfones are capable of reacting with both cysteine and lysine residues, depending on the sulfone substituents and the targets. What advantages and disadvantages do covalent inhibitors have?