Coumarin (2H-1-benzopyran-2-one) nucleus and it's natural, as well as synthetic derivatives, has been a field of interest due to its unique tendency to adopt varying categories of substitutions which provides the basis for modifying this nucleus for multidisciplinary actions. The extensive literature review reflects that coumarin derivatives have been synthesized by several structural modifications and exhibit numerous activities like antiinflammatory, anti-tumor, anti-HIV, anticoagulant, antimicrobial, antioxidant, anti-hepatitis, hepatoprotective, anti-pyretic, analgesics, antithrombotic, vasodilatory, anti-mutagenic, antioxidant, anti-fungal, anti-viral, anti-hypertensive, anti-tubercular, anti-convulsant, anti-adipogenic and antihyperglycemic. They also inhibit lipooxygenase, cyclooxygenase, MAO-A, MAO-B, and TNF-alpha enzymes. The purpose of this study is to review the anti-inflammatory potentials of coumarins and to generate a comparative SAR that may support to improve their anti-inflammatory activity by newer and potent diverse structural modifications of the coumarin nucleus. The review shows that wide varieties of coumarin derivatives have been synthesized and have shown anti-inflammatory potentials. These derivatives can be further modified with the help of SAR generated in the present work to improve the anti-inflammatory potentials of the versatile coumarin nucleus. INTRODUCTION: Coumarin owes their class name to 'Coumarou,' the vernacular name of the tonka bean; consist of fused benzene and α-pyrone rings 1. It represents a vast family of compounds naturally found in plants. There are four main coumarin sub-types which include simple coumarins, furanocoumarins, pyrano coumarins, and pyrone-substituted coumarins 2. The simple coumarins are the hydroxylated, alkoxylated, and alkylated derivatives of the parent compound, coumarin, along with their glycosides.