The presence of antibiotics in the natural systems affects the environment. Their incidence has led to the increased emergence of antibiotic resistant microbes. These multi-drug resistant organisms persist and spread globally, thereby causing clinical failures in treating infections and health crises. Treatment of such infections caused by multi-drug resistant bacteria has been compromised although it is imperative that such resistance has been attributed to various molecular and cellular changes in the bacteria. This review focuses on the various cellular and molecular modifications that happen in a bacterial cell in general. It is important for us in order to understand these mechanisms for the better management of the antibiotics.