Scientific research is an open-ended quest where success usually triumphs over failure. The tremendous success of science obscures the tendency for the non-linear discovery process to take longer and cost more than expected. Perseverance through detours and past setbacks requires a significant commitment that is fueled by scientific optimism; the same optimism required to overcome challenges simultaneously exacerbates the very human tendency to continue a line of inquiry when the likelihood of success is minimal, the so-called sunk-cost bias. This Viewpoint Article shows how the psychological phenomenon of sunk-cost bias influences medicinal, pharmaceutical, and organic chemists by comparing how the respective industrial and Academic practitioners approach sunk-cost bias; a series of interviews and illustrative quotes provide a rich trove of data to address this seldom discussed, yet potentially avoidable research cost. The concluding strategies recommended for mitigating against sunk-cost bias should benefit not only medicinal, pharmaceutical, and organic chemists but a wide array of chemistry practitioners.