Reactions between thiols and various types of unsaturations or electrophiles, referred to as thiol-X chemistries (Scheme 1) [4], have been used extensively to modify everything from small molecules, polymers, and particles to macroscopic substrates [5] and [6]. The success of these types of reactions is due to their “click chemistry” nature, as they are highly efficient and selective, produce no or few by-products, and can be conducted under mild reaction conditions. This class of reactions is a highly popular approach to the modification of biological and biomimetic moieties, as they provide a more biologically friendly approach to the modification of materials. These types of reactions do not require toxic catalysts such as those required in the copper-catalyzed Huisgen [3+2] cycloaddition reaction between azides and alkynes, and they are tolerant to air and water (to a certain extent), which makes them very appealing to provide the facile modification of peptides and proteins. The use of thiol-X chemistry to modify peptides and proteins is not entirely new. Cysteine, a natural amino acid, bears a convenient primary thiol group, making it an ideal substrate for modification in peptides and proteins. This type of chemistry has allowed researchers to expand the application scope of these well studied materials.