Essential oils (EOs) have been used therapeutically for centuries. In recent decades, randomized controlled (clinical) trials have supported efficacy in specific therapeutic indications for a few of them. Some EOs, their components or derivatives thereof have been approved as drugs. Nevertheless, they are still considered products that are mainly used in complementary and alternative medicine. eo components occupy a special niche in chemical space, that offers unique opportunities based on their unusual physicochemical properties, because they are typically volatile and hydrophobic. Here we evaluate selected physicochemical parameters, used in conventional drug discovery, of EO components present in a range of commercially available EOs. We show that, contrary to generally held belief, most EO components meet current-day requirements of medicinal chemistry for good drug candidates. Moreover, they also offer attractive opportunities for lead optimization or even fragment-based drug discovery. Because their therapeutic potential is still under-scrutinized, we propose that this be explored more vigorously with present-day methods.Over the past few decades, drug discovery has shifted mainly to high-throughput screening of large chemical libraries while research on natural products has diminished 1,2 . Reasons for this are among others: (i) the legitimate concerns about the United Nations Convention on Biological Diversity and the Nagoya protocol which regulates the sovereign rights of genetic resources, resulting in many years of legal uncertainty regarding derived rights 3,4 . (ii) The difficulty of patent protection for natural products, especially since the publication of the "Guidance for Determining Subject Matter Eligibility of Claims Reciting or Involving Laws of Nature, Natural Phenomena, & Natural Products" 5,6 . (iii) The belief that natural products are somehow incompatible with high-throughput screening, and (iv) that they are difficult to isolate or synthesize 7 . At the same time, some compound collections are designed to mimic natural products, because these also offer clear advantages; for example, they exhibit a wide range of pharmacophores, show a high degree of stereochemistry and are metabolite-like 2,4,8-13 . However, recent technical developments and increased legal certainty have led to a renewed interest in natural product drug discovery 1,2,4,7,12,[14][15][16] . This is further strengthened by the 2015 Nobel Prize in Physiology or Medicine for natural product research on artemisinin; a sesquiterpene lactone with anti-malarial properties from the plant Artemisia annua, and on avermectins; macrocyclic lactones with potent anthelmintic and insecticidal properties derived from the soil bacterium Streptomyces avermitilis 7,17 .Companies have made great efforts to increase the chemical diversity of their compound collections used for drug discovery, but at the same time to reduce especially late-stage attrition; as a result the composition of these collections is increasingly shaped, or even dictat...