Nonsteroidal anti-inflammatory drugs available in the market suffer from side-effects like gastric ulceration, hepatotoxicity, renal toxicity, etc. Selective COX-2 inhibitors have been developed to reduce the side-effects, but unfortunately suffer from severe cardiovascular toxicity. As a result, several selective COX-2 inhibitors have been withdrawn from the market. Thus to improve the efficacy with reduced side-effects many strategies were developed. The free carboxylic group of the NSAIDs was modified into various acid derivatives to reduce gastric ulceration. Modifications of the existing anti-inflammatory drugs were carried out by various research groups so that the efficacy of the drugs improves along with selectivity. This review covers changes and structural modifications of various anti-inflammatory agents. Synthesis of various derivatives of NSAIDs was reported in the literature review. The article also summarizes the synthesis of the molecules using microwave assisted synthesis. Computational studies (i.e. QSAR and Docking analysis) along with information about various novel moieties acting against reported inflammation is also discussed in the article.