The so-called Hippocratic injunction to do no harm has been an axiom central to clinical pharmacology and to the education of medical and graduate students. With the recent reexamination of the nature and magnitude of adverse reactions to drugs, the purposes of this research and review were to discover the origin of this unique Latin expression. It has been reported that the author was neither Hippocrates nor Galen. Searches of writings back to the Middle Ages have uncovered the appearance of the axiom as expressed in English, coupled with its unique Latin, in 1860, with attribution to the English physician, Thomas Sydenham. Commonly used in the late 1800s into the early decades of the 1900s, it was nearly exclusively transmitted orally; it rarely appeared in print in the early 20th century. Its applicability and limitations as a guide to the ethical practice of medicine and pharmacological research are discussed. Despite insufficiencies, it remains a potent reminder that every medical and pharmacological decision carries the potential for harm.