Art is always a bonus to synthesis . . . . the artistic aspect of synthesis, beautiful and marvelous as it is, should not be a justification for carrying out a total synthesis. If your problem is truly essential then you don't care about the elegance. The more essential your first E is, the less important your last E becomes." 1 "Will we be able to recapture the many millions of presumed 'transient'natural products that were evolutionarily de-selected along the paths that eventually led to the natural products synthesized on Earth today? . . . I cannot imagine that in a young synthetic chemist's lifetime, it will not be accomplished." 2 Organic Synthesis, quo vadis? 3 has been a phrase, perhaps in a more modern language, on the lips of the practitioners of this demanding science-art, undoubtedly from the earliest times 4 but more vigorously in the last two decades. 5 Comparison of achievements of yesterday 6 and today 7 suggests progress in our abilities to construct molecules of complexity, with higher stereocontrol, faster analysis, and greater prediction of eventual success. However, the practical aspects, on any scale, of brevity, efficiency, safety, eco-consciousness, and energy-and resource-frugality remain, as noted by a major synthetic craftsman, 8 crudely addressed. The Y2K symbolism is perhaps also appropriate for urgently dedicating our efforts to making headway in the solution of these interrelated goals.Our central science 5a progresses on fronts of method development and total synthesis with a great deal of cross-talk and interdependency (see Fig. 1). The burgeoning literature of new methods suggests that 70% are not repeated, perhaps even in the original laboratories, a situation with dire consequences for ascertaining true yield ranges and reproducibility a la the Org. Syn. religion. Furthermore, as judged from a cursory glance of tables in recent journals, much is left to be desired in giving confidence to the user that a method has generality (substrate diversity, FG and steric tolerance, catalyst or reagent minimization, and temperature and solvent optimization). Although the beauty of judiciously modeled use of PGs is to be applauded, 9 FG protection is a continuing embarrassment and annoyance. Synthetic chemists are challenging the dogma by daring the multi-FG molecules to behave in the manner desired. Ugi multicomponent reactions 10 and combinatorial synthesis 11 will undoubtedly soon influence the PG-expediency problem. In industry, statistical programs 12 at times drive optimization of reactions thus meeting the normal intense time constraints to produce mulit-kg of commercial substances.Atom-economy, a term coined by another influential synthetic chemist, 13 has brought awareness of an issue to academic scientists which their industrial process and development colleagues un-