OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for antimicrobial therapy for patients with severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: Since the prompt institution of therapy that is active against the causative pathogen is one of the most important predictors of outcome, clinicians must establish a system for rapid administration of a rationally chosen drug or combination of drugs when sepsis or septic shock is suspected. The expanding number of antibacterial, antifungal, and antiviral agents available provides opportunities for effective empiric and specific therapy. However, to minimize the promotion of antimicrobial resistance and cost and to maximize efficacy, detailed knowledge of the likely pathogens and the properties of the available drugs is necessary for the intensivist.