The primary aim of the EU, with the registration of herbal medicinal products (HMPs), is the protection of the European citizens from fraudulent and unsafe products. In fact, the EU is rather rigorous on this issue and therefore manufacturers are obliged to deal with safety issues. Although a Traditional Herbal Medicinal Products would have been in circulation for centuries, it is possible that with time, research proves the presence of toxic substances within the product. As herbal remedies are derived from nature, uneven conditions of growth and different varieties of a specific plant species may contribute to the emergence of previously-insignificant plant toxins. This has been also experienced with herbs and plants that are used for culinary purposes. Therefore to ensure the safety of herbal medicines, proof can be demonstrated by employing a battery of in vitro and in vivo tests. ; peer-reviewed