Thiophene, a five membered heterocycle is considered as biologically important dynamic scaffold that holds wide range of biological activities. The fruitful application of Cephoxitin as antimicrobial, Thenaldine as anti inflammatory, Ralitrexed as anticancer and Erdosteine as antioxidant proved the potential of thiophene moiety. Diverse biological response profile has pulled in consideration of many researchers to investigate this heterocycle to its multiple potential against several activities. This review is complementary to previous reviews and focuses to review the work reported on antimicrobial activities of thiophene derivatives.