The increasing presence of drug-resistant bacterial infections among hospitalised patients has resulted in greater numbers of patients receiving inappropriate antimicrobial treatment. This has led to the development of a novel paradigm guiding the administration of empirical antimicrobial therapy for patients with serious infections in the hospital setting. Antibacterial de-escalation is an approach to antibacterial utilisation that attempts to balance the need to provide appropriate, initial antibacterial treatment while limiting the emergence of antibacterial resistance. The goal of de-escalation is to prescribe an initial antibacterial regimen that will cover the most likely bacterial pathogens associated with infection while minimising the emergence of antibacterial resistance. Antibacterial resistance is minimised by narrowing the antibacterial regimen once the pathogens and their susceptibility profiles are determined, and by employing the shortest course of therapy clinically acceptable.