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From ancient times, natural products have been continuously used as therapeutic agents in the treatment of various ailments. Many drugs from the natural origin are available in the market as potent medicines. Over expression of cyclooxygenase-2 (COX-2) enzyme is associated with various physical disorders like various types of inflammations associated with cardiovascular diseases or malignancies. The COX-2 inhibitory activity of many active constituents derived from plants is well established in the literature. These include coumarins, alkaloids, flavonoids, cinnamates, stilbenes and xanthines. In the present review, an attempt has been made to summarize applications of compounds since 2000 obtained from natural sources as COX-2 inhibitors. A brief synthetic methodology to access these natural product derivatives has been highlighted along with the Structure Activity Relationship (SAR)