Since the landmark publications of the first directed aldol addition reaction in 1973, the site, diastereo-, and enantioselective aldol reaction has been elevated to the rarefied status of being both a named and a strategy-level reaction (the Mukaiyama directed aldol reaction). The importance of this reaction in the stereoselective synthesis of untold numbers of organic compounds, both natural and unnatural, cannot be overstated. However, its impact on the field extends beyond the impressive applications in synthesis. The directed aldol reaction has served as a fertile proving ground for new concepts and new methods for stereocontrol and catalysis. This Minireview provides a case history of how the challenges of merging site selectivity, diastereoselectivity, enantioselectivity, and catalysis into a unified reaction manifold stimulated the development of Lewis base catalyzed aldol addition reactions. The evolution of this process is chronicled from the authors’ laboratories as well as in those of Professor Teruaki Mukaiyama.