This article takes its cue from the original work of sir Alexander Fleming on penicillin, published in the first issue of Recenti Progressi in Medicina in 1946 and reproduced here on the occasion of the approaching 70-year anniversary of the journal. The path that brought Fleming to the discovery of penicillin, one of the major milestones in the history of clinical pharmacology, provides insight for a range of considerations: the painstaking efforts of researchers, the contribution from accidental findings, and the dissemination of study results. Although the discovery of penicillin has changed the course of medicine, the benefits deriving from such an important advance are most likely to be offset by the overprescription of antibiotics, which is the leading cause of antimicrobial resistance and one of the most serious public health problems of our time.