In light of the growing global health problem associated with osteoarthritis, herbal remedies have become an important research focus in the scientific and medical community, and numerous studies have been published to identify their biological effects and mechanisms in vitro and in vivo. This review is a snapshot of the most recent clinical trials on the efficacy of medical plant extracts in knee osteoarthritis patients, and provides relevant background information on the biological mechanisms that may underlie the clinical observations. Therefore, we performed a PubMed literature survey and discussed a selection of clinical trials in the field, with special attention being drawn to the design and outcome measures of the studies. We further spotlighted on issues relating to the efficacy and safety of the plant extracts and discussed major challenges for upcoming studies in the field, which include the need for rigorously designed in vivo and in vitro studies, as well as the elucidation of potential additive effects and structure-modifying activities beyond symptom relief.