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The fresh or dried stems of many Dendrobium species are well known as one of the most expensive tonics in traditional Chinese medicine. Documented as a “superior grade” herbal medicine in the ancient text “Shen Nong’s Herbal Classic”, Dendrobium has been used for thousands of years and is now a popular health food worldwide. The main chemical components of Dendrobium are alkaloids, aromatic compounds, sesquiterpenoids and polysaccharides, with multiple biological activities, including immunomodulatory, neuroprotective and anti-tumor effects, etc. Various qualitative and quantitative methods have been developed for the quality evaluation of Dendrobium. In this review, the research progress since the 1930s relating to the chemistry, bioactivity and quality control of Dendrobium is summarized, existing problems and prospects are also discussed.