This study uses historical texts in order to obtain information on the natural products used in traditional medicines in European/Mediterranean therapeutics over the last two millennia. The information obtained may lead to new directions in the area of drug discovery, as recent research has demonstrated the continued promise of looking to natural products for bioactive compounds. Researchers have increasingly turned to traditional medicines to provide clues as to which natural products to investigate, but the oral traditions on which much of this medical knowledge rests are often unstable. Thus researchers have been prompted to use historical medical texts, as this study does, to find potential sources of new drugs. This study uses twelve Mediterranean/European medical texts from the 5th century BC to the 19th century AD to compile a list of the most commonly used “simples”–or single action drugs substances–used in therapeutics in traditional European medicine. This list was then compared to present-day herbal pharmacopoeia as represented by the National Institutes of Health (NIH). This study finds that traditional European materia medica was based on a Dioscoridean tradition that lasted through the 19th century with remarkably little variation, but is significantly different from the present-day herbal pharmacopoeia according to the NIH. The most prominent simples in the European/Mediterranean medical tradition can provide clues to further bioactive compounds that have not as of yet been fully exploited for their potential, but were clearly of great use in the past.