The Sharpless Lab pursues useful new reactivity and general methods for selectively controlling chemical reactions. Though the focus has progressed from regio- to stereo- to asymmetric and, now, to connectivity control, the core chemistry remains unchanged: the oxidation of olefins, that single most versatile, powerful and reliable (KBS argues) chemical transformation. The Sharpless Lab was the first academic chemistry group with robotics, and the lesson from the combinatorial numbers game was the primacy of reliability. "Click" chemistry was the Sharpless Lab's response: a set of powerful, virtually 100% reliable, selective reactions for the rapid synthesis of new compounds via heteroatom links (C-X-C). Click chemistry is integral now to all research within the Sharpless Lab.