Substituted N-heterocyclic compounds are found to have various medicinal properties, therefore they are widely used in pharmaceutical industry. In context with Green Chemistry, in this book, we have reported the synthesis of substituted derivatives of pyridine, pyrimidine and isoxazoline using eco-friendly approach which offers a reduction or even elimination of solvent use and recovery of solvent. To provide the eco-friendly approach to the synthesis procedures we used microwave irradiation (MWI) as a non-conventional energy source, using different catalysts such as CoCl2, K-10 Montmorillonite clay and Zeolite ZSM-5 as they provide enhanced reaction rates, improved product yields, reduced reaction time duration and thus facilitates the formation of products under milder reaction conditions with a consequent increase in yield. Synthesized compounds were characterized by means of FTIR, PMR, CMR, Mass spectral and UV analysis. The synthesized pyridine, pyrimidine and isoxazoline derivatives were screened for their antimicrobial activity using disc diffusion method against certain bacteria and fungi and found to have better antibacterial and antifungal activity.