Rhododendron, an important and cosmopolitan genus of the Ericaceae family with ca. 850 species, is distributed in the Northern Hemisphere mainly in Asia. Phytochemical and biological investigations on this genus date back to 1960, and since then, systematic and comprehensive studies worldwide have isolated hundreds of secondary metabolites, mainly flavonoids and diterpenoids, some of which show significant bioactivities. Some Rhododendron species have been used in traditional medicine: e.g., the dried stems, leaves, and flowers of R. spinuliferum for eliminating phlegm, relieving cough, and as an anti-asthmatic; the dried leaves of R. dauricum (known as Manshanhong in China) as an expectorant and for treating acute and chronic bronchitis, with the MeOH extract of its leaves and twigs showing significant anti-HIV activity; the flowers and fruits of R. molle as analgesics; and several other species such as R. ponticum, R. chrysanthum, R. ferrugineum, R. cinnabarium, and R. collettianum for various inflammatory conditions and pain. Prompted by these medicinal properties, this review provides a comprehensive and systematic analysis of Rhododendron from phytochemical and biological viewpoints. To the best of our knowledge, since 1990 there have not been in-depth reviews on this genus from these viewpoints, so this review covers research on Rhododendron in the last 20 years (1990 to November 2009). Another aim is to provide a platform for natural product chemists to evaluate the biological activities of the isolates from Rhododendron, as the structural characteristics of isolates with remarkable biological activities may provide valuable information for the design of new drug molecules. During 1990 to November 2009, phytochemical and biological studies on Rhododendron have resulted in the isolation and characterization of ca. 208 secondary metabolites (1–208), including monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, steroids, coumarins, flavonoids, and others, with flavonoids being the most frequent and diterpenoids the second most frequent kind of secondary metabolites.