Since prehistoric times, humans have understood that plants possessed healing properties. The knowledge of herbal medicine has been accumulated for millennia by traditional healers and has been passed down from generation to generation. Phytotherapy was used as the main therapy until the 18th century. Even today, between 40% and 80% of pharmaceuticals are phytochemicals or of plant origin and many of these have significantly changed or are still changing medical therapy. Most people in the world are or have been treated with phytochemicals or drugs derived from phytochemicals. Examples include antineoplastic agents (vinblastine, vincristine, etoposide, teniposide, paclitaxel, irinotecan, topotecan), antibiotics and antivirals (cephalosporins and oseltamivir), antiparasitic drugs (quinine and artemisinin), Intensive Care Unit (ICU) drugs (morphine, neuromuscular blockers, ephedrine), cardiovascular drugs (digoxin, quinidine, atropine, reserpine), antidiabetics (metformin), and many others. Many of these agents are included in the WHO list of essential medicines. Plant-derived medicines have changed human history, contributing fundamentally to the survival and improvement of our species’ life expectancy. Phytochemicals, derived from interactions between plants and the environment, are substances often created over millennia. If humans had not drawn on these substances for medical therapy, they probably would never have been able to produce substances so complex and effective in treating disease. Since knowledge of the healing properties of plants is present in traditional medicines, ancient manuscripts should be studied as potential sources of contemporary pharmacotherapy. Unfortunately, in recent years several trends have started to threaten biodiversity and consequently also phytochemical resources. From this perspective, the “One Health” approach is further justified and could also encourage the discovery of new revolutionary phytochemicals.