Bacterial enteric pathogens are by far the most dominant scourge of mankind. There are more than 200 million cases and 3 million deaths caused by these bacteria every year. Before the antimicrobial era, there were pandemics of enteric diseases which sometimes swept away whole populations. Advent of antimicrobial era provided a tool in the hand of mankind to fight this menace. In the beginning the results were promising and there was optimism of a decisive victory against disease causing bacteria. But the reality dawned within a couple of decades when antimicrobial resistance started to emerge and every new antimicrobial was generally knocked out in a couple of years. It became apparent that these bacteria held a distinct advantage because of very fast evolution rate due to relatively simple and small genome and short generation time. Currently, we are always playing a catch up game because the enemy is always ahead. The emergence of multiple drug resistance (MDR) has aggravated the situation and there is a distinct possibility that some of these menacing bugs may get out of control and situation of pre-antimicrobial era may return. Recently, a new term extreme-drug resistance (XDR) has been coined. This refers to bacteria resistant to all available drugs. This aptly summarizes the situation we are facing today. This catastrophe can only be avoided by putting more efforts in developing new concepts and products. This chapter is an effort to encompass the properties of these pathogens, the antimicrobials currently in use and the mechanisms of drug resistance evolved by these formidable bacteria.