Increasing rates of antimicrobial drug resistance in the community and in the ICU imperil our ability to care for patients with sepsis and septic shock. In this session, we will review the clinical features that clinicians can use to guide rational antimicrobial drug use, new and emerging diagnostic tests that help us make the right choice of drugs more rapidly, and the data for novel antimicrobial agents, including beta-lactam/beta-lactamase inhibitors and tetracycline derivates, that may support the care of infected patients in the ICU.