Herbal medicine is the use of medicinal plants for prevention and treatment of diseases: it rangesfrom traditional and popular medicines of every country to the use of standardized and tritatedherbal extracts. Generally cultural rootedness enduring and widespread use in a traditionalmedical system may indicate safety, but also efficacy of treatments, especially in herbal medicinewhere tradition is almost completely based on remedies containing active principles at very lowand ultra low concentrations or relying on magical-energetic principles. The efficacy and safetyassessments of medicines, whether modern or herbal, invariably encounter challenges orproblems during the course of pre-clinical and clinical research. Some of the challenges inevidence-based herbal medicinal research are unique, and the researcher must be cognizant ofthem in order to safeguard the quality of the data obtained. Key challenges are: the quality of rawmaterials; appropriateness of biological/pharmacological activity assessment methodology, anddata interpretation; standardization methodology; pharmacokinetics and bioavailability of activeconstituents and metabolites; clinical dosage formulation/production; and clinical study designsand outcome measures.