The fight against the emergence and spread of antibiotic resistant organisms in hospitals demands a wide-ranging and comprehensive strategy of attack. Although a multifaceted approach is required, the following discussion will be restricted to the translation of new molecular techniques into diagnostic tests, and initiatives to optimize antibiotic prescribing in hospitals. An ideal rapid test would determine categorically whether a pathogen is present or not in a clinical sample, and if so, the identification and antibiotic susceptibility, all within 1–2 hours. Widespread use of such tests, and their translation into portable “near patient tests,” will undoubtedly have significant consequences regarding patient management and control of antibiotic resistance. In the wider hospital setting, developments in information technology and new applications of management, organization, and service delivery must be adopted to optimize antibiotic prescribing. By combining timely diagnostics with the larger-scale hospital systems for the delivery of care, we may start to win the battle against antibiotic resistance.