The search of novel anti-inflammatory agent is not considered as an ending process, since most of the clinically used anti-inflammatory drugs such as NSAIDs, Coxibs and GCs are allied with considerable toxicity. However, numerous approaches were used to overcome the toxicity level such as co-administration with suitable agent/substance which provides protection against toxicity as well to synthesise new potent and safe anti-inflammatory drug. Although the drug treatment has been improved steadily but yet, it is still a challenge for the medicinal chemists to identify more potent therapeutic agents to treat or reduce the symptoms of inflammatory diseases. A variety of N-heterocyclic analogs are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal and anti-HIV. The present review summarizes the synthetic methodology and therapeutic potential of some N-heterocyclic analogs as potent anti-inflammatory agents.