Karl Barry Sharpless is an American chemist at Scripps Research and one of only five individuals to have won two Nobel Prizes, both in Chemistry. He received the 2001 prize for his work on chirally catalysed oxidation reactions and a share of the 2022 prize, with Carolyn Bertozzi and Morten Meldal, for the development of click chemistry and bioorthogonal chemistry. His asymmetric oxidation methods — the Sharpless epoxidation of allylic alcohols, the Sharpless asymmetric dihydroxylation, and asymmetric aminohydroxylation — gave synthetic chemists reliable, predictable ways to install chirality and became indispensable in the manufacture of pharmaceuticals, agrochemicals, and fine chemicals. Around 2001 Sharpless articulated the concept of click chemistry: a philosophy of building molecules from a small set of near-perfect, modular, high-yielding reactions that work under simple conditions, with the copper-catalysed azide–alkyne cycloaddition as its flagship transformation. This reframing accelerated drug discovery, materials synthesis, surface functionalization, and bioconjugation. More recently he introduced sulfur(VI) fluoride exchange (SuFEx) as a second-generation click reaction. Sharpless earned his PhD at Stanford under Eugene van Tamelen, held professorships at MIT and Stanford, and has led a laboratory at Scripps Research, where his in-situ click chemistry approach generates high-affinity enzyme inhibitors by letting the biological target template its own ligand.