Green chemistry has become a hot topic and the focus of not only many companies but also researchers.

Since their introduction as a new strategy for synthesizing diverse chemotypes, sulfur(VI)–fluoride exchange (SuFEx) transformations have found applications ranging from polymer chemistry and covalent probe development to bioconjugation tools and chemistries for the synthesis of compound libraries. The collection of SuFEx reactions has expanded significantly since their introduction as a concept, comprising functionalities with varying reactivities towards different nucleophiles; thus, enabling the generation of a wide array of sulfur-containing functional groups for the linkage of structural elements in diverse chemotypes. In this review, we focus on the most recent developments in the use of SuFEx chemistry as a means for the preparation of compound libraries for biological screening as well as the introduction of SuFEx hubs into various biomolecules.