The concept of click chemistry matured simultaneously in different laboratories around the world in the 1990’s. There was an urgent need for quantitative chemical reactions/molecular LEGO® to cope with the pressure from combinatorial science to synthesize, screen and identify one out of thousands – millions of compounds. During investigations of combined Peptide diversity, we more or less serendipitously discovered the CuAAC click reaction in 2001. The mechanism of the reaction will be discussed and its application in a variety of studies involving immobilization, mimicry, structural control and protein ligation will be presented. The more existential aspects of our fundamental understanding of chemistry, the importance of serendipity, and our pledge to the young to study chemistry for a better future, will also be discussed.