As from the 6th century BC Graeco-Roman medical therapy comprised three components, viz. diet and healthy lifestyle (regimen), surgery and medicaments (pharmacotherapy), of which the latter was the oldest. Although the Corpus Hippocraticum (5th century BC), with minor Egyptian influence, contained no text of medicines as such, and seemed to prefer regimen to medicaments, it nevertheless laid the foundation for the empirical use of pharmacotherapy (free of superstition and magic) for the next millennium. The first Greek herbal was produced by Diocles in the 4th century BC, when the botanist Theophrastus also wrote his classic works on plants which contained a significant contribution on herbal medicines. The Alexandrian Medical School systematized and expanded Hippocratic medicine, and Herophilus introduced compound preparations. The concept that medicaments cure illness by restoring the bodily balance of humours and primary properties was largely perpetuated, but new views on physiology were gradually emerging. Unfortunately the bulk of original contributions from Hellenistic doctors are lost to posterity and only known to us through the writings of for example Celsus and Galen in Roman times. The interesting history of theriac, the so-called universal antidote, is reviewed. In the 1st century Dioscorides produced his Materia Medica which remained an authoritative pharmacopoeia up to modern times. Galen’s empiric views on pharmacotherapy (2nd century), still largely based on Hippocrates, became dogma in Medieval times, but mysticism and superstition gradually swept back into medicine. Retrospectively it is clear that with the exception of certain analgesics and narcotics like opium, Graeco-Roman medicaments were pharmacologically inert (even toxic) and obtained positive results largely through a placebo effect.