Macromolecular X-ray crystallography has undergone a dramatic and astonishing transformation since its inception in mid 1950s, almost exclusively owing to the developments in three other fields: computer science; synchrotron radiation; and molecular biology. The process of structure solution from a single crystal, provided the quality of diffraction data is adequate, has been shortened from many years to hours, if not minutes. Yet, in spite of the exponential increase in the available structural information (~120,000 structures in the Protein Data Bank today), many fundamental problems continue to be the subject of scientific controversy. This article contains personal recollections of the author, pertaining to two research projects – conducted nearly four decades apart – both of which touch upon such long standing discussion of the Monod-Wyman-Changeux theory of cooperativity (or ‘conformational selection’) vs the Koshland-Nemethy-Filmer theory of ‘induced fit’. It is dedicated to Dr. Alexander Wlodawer on his 70th birthday, with best wishes of continuing success.