A juicy tale based on many fruitless efforts: The determination of the structure of the natural product santonin and its transformation product, santonic acid (see formulas), occupied organic chemists for nearly 80 years. The story of these efforts captures the early days in the practice of structure determination, and shows how difficult this exercise was before the availability of the powerful tools of IR and NMR spectroscopy, mass spectrometry, and the ultimate weapon, X‐ray crystallography.