In the modern scenario, the quinolone scaffold has emerged as a very potent motif considering its clinical significance. Quinolones possess wide range of pharmacological activities such as anticancer, antibacterial, antifungal, antiprotozoal, antiviral, anti-inflammatory, carbonic anhydrase inhibitory and diuretic activity etc. The versatile synthetic approaches have been successfully applied and several of the resulted synthesized compounds exhibit fascinating biological activities in numerous fields. This has prompted to discover quinolone-based analogues among the researchers due to its great diversity in biological activities. In the past few years, various new, efficient and convenient synthetic approaches (including green chemistry and microwave-assisted synthesis) have been designed and developed to synthesize diverse quinolone-based scaffolds which represent a growing area of interest in academic and industry as well as to explore their biological activities. In this review, an attempt has been made by the authors to summarize (1) One of the most comprehensive listings of quinolone-based drugs or agents in the market or under various stages of clinical development; (2) Recent advances in the synthetic strategies for quinolone derivatives as well as their biological implications including insight of mechanistic studies. (3) Further, the biological data is correlated with structure-activity relationship studies to provide an insight into the rational design of more active agents.