OBJECTIVE The aim of this article is to outline developments in the three cornerstones of treatment of intra-abdominal infections during critical illness: source control; antimicrobial therapy; and mitigation of deranged immune and coagulation responses. RESULTS Although adequate source control remains the goal of mechanical management of intra-abdominal infections, neither planned re-laparotomy nor open-abdomen management appears to offer a survival benefit as compared with on-demand re-laparotomy. Novel approaches to restoration of a functional gastrointestinal tract have emerged as alternatives to more invasive surgery. A persistent increase in the prevalence of intra-abdominal infections caused by multidrug resistant pathogens has led researchers to investigate shorter-course antimicrobial therapy and other antibiotic administration strategies with encouraging initial results. Therapy with recombinant human activated protein C should now be considered for patients with severe abdominal sepsis associated with a high risk of death. CONCLUSIONS Because randomized controlled trials of intra-abdominal infections involve critically ill patients infrequently, only limited evidence-based recommendations regarding the management of these patients may be drawn. Therapy should focus above all else on timely obtainment of adequate source control, in conjunction with judicious use of antimicrobial therapy dictated by individual patient risk factors for infection with multidrug resistant pathogens.