Free-energy calculations have had a revolutionary effect on computational chemistry. In conjunction with molecular dynamics and Monte Carlo simulations, they have enabled the calculation of free energy changes for wide-ranging phenomena including fundamental solution thermodynamics, solvent effects on equilibria, activation barriers for reactions in solution, host-guest binding, and drug lead optimization. An overview of our free energy efforts starting in 1981 with umbrella sampling for conformational equilibria, continuing to the FEP calculations in 1985 for the ethane to methanol mutation, and leading to recent discoveries of extraordinarily potent inhibitors of the main protease of SARS-CoV-2 will be presented.