Probiotics are living microorganisms which, when ingested in adequate amounts, provide health benefits to the host. The mechanisms of these benefits include improved gastrointestinal barrier function, modification of the gut flora by inducing host cell antimicrobial peptides, releasing probiotic antimicrobial factors, competing for epithelial adherence, and immunomodulation to the advantage of the host. In the intensive care unit, probiotics appear to provide benefits in antibiotic-associated diarrhea, ventilator-associated pneumonia, and necrotizing enterocolitis. With increasing rates of antibiotic resistance among common nosocomial pathogens and fewer new antibiotics in the research pipeline, increasing attention has been placed on nonantibiotic approaches to the prevention and treatment of nosocomial infections. Existing studies of probiotics in critically ill patients are limited by heterogeneity in probiotic strains, dosages, duration of administration, and small sample sizes. Although probiotics are generally well tolerated and adverse events are very rare, the results of the PROPATRIA (Probiotics Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) trial highlight the need for meticulous attention to safety monitoring. Better identification of the ideal characteristics of effective probiotics coupled with improved understanding of mechanisms of action will help to delineate the true beneficial effects of probiotics in various disorders.