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Appropriate antimicrobial therapy is essential to ensuring positive patient outcomes. Inappropriate or suboptimal utilization of antibiotics can lead to increased length of stay, multidrug-resistant infections, and mortality. Critically ill intensive care patients, particularly those with severe sepsis and septic shock, are at risk of antibiotic failure and secondary infections associated with incorrect antibiotic use. Through the initiation of active empiric antibiotic therapy based upon local susceptibilities, daily evaluation of signs and symptoms of infection and narrowing of antibiotic therapy when feasible, providers can streamline the treatment of common intensive care unit (ICU) infections. Optimizing antibiotic dosing through prolonged infusions can be beneficial in intensive care populations with altered pharmacokinetics. Antimicrobial stewardship teams can assist ICU providers in managing and implementing these tactics. This review will discuss the current literature on antibiotic use in the ICU applying antimicrobial stewardship strategies. Based upon the most recent evidence, ICUs would benefit from employing empiric guidelines for antibiotic use, collecting appropriate specimens and implementing molecular diagnostics, optimizing the dosing of antibiotics, and reducing the duration of total therapy. These strategies for antibiotic use have the potential to enhance patient care while preventing adverse outcomes.