Publisher Summary This chapter discusses activation and coupling chemistry. Some of the reagents discussed are not themselves cross-linking or modification compounds, but may be used to form active intermediates with another functional group. These active intermediates subsequently can be coupled to a second molecule that possesses the correct chemical constituents, which allows bond formation to occur. Every chemical modification or conjugation process involves the reaction of one functional group with another, resulting in the formation of a covalent bond. The creation of bioconjugate reagents with spontaneously reactive or selectively reactive functional groups forms the basis for simple and reproducible cross-linking or tagging of target molecules. This chapter is meant to function as a ready-reference database for learning or review of bioconjugate chemistry. In this regard, a reaction is described and a brief of its properties and uses, and a visual representation of the chemistry of bond formation are illustrated.