This article reviews studies dealing with gut barrier dysfunction following major trauma and alcohol exposure. An association between alcohol exposure and traumatic injury has been recognized in many studies. The gut is the major reservoir of bacteria within the body but, under healthy conditions, it maintains a barrier which prevents these bacteria from crossing the intestinal lumen. The findings reviewed herein indicate that this barrier is lost in conditions such as major trauma and alcohol exposure. Furthermore, studies also indicate that alcohol intoxication at the time of injury causes a further deterioration in intestinal barrier function as determined by intestinal permeability and bacterial translocation. A precise mechanism for impaired barrier function following alcohol exposure, either alone or in combination with major trauma or burn injury, remains unknown. However, the findings discussed in this article indicate that this could result from: (i) an increase in bacterial growth; (ii) a decrease in blood flow; (iii) an increase in inflammatory mediators such as cytokines and chemokines; and (iv) an increase in the release of superoxide anions and proteases by neutrophils.