Small intestinal bacterial overgrowth is common in intestinal failure. Its occurrence relates to alterations in intestinal anatomy, motility, and gastric acid secretion. Its presence may contribute to symptoms, mucosal injury, and malnutrition. Relationships between bacterial overgrowth and systemic sepsis are of potential importance in the intestinal failure patient because the direct translocation of bacteria across the intestinal epithelium may contribute to systemic sepsis: a phenomenon that has been well established in experimental animal models. The accurate diagnosis of bacterial overgrowth continues to present a number of challenges in clinical practice and especially so among patients with intestinal failure. The management of patients with bacterial overgrowth remains, for the most part, primarily empiric and comprises antibiotic therapy and correction of any associated nutritional deficiencies. Although evidence from experimental animal studies consistently indicates that probiotics exert barrier-enhancing, antibacterial, immune-modulating, and anti-inflammatory effects, which all could be benefits in small intestinal bacterial overgrowth and intestinal failure, their role in human beings remains to be evaluated adequately.