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