Infectious complications are the most common cause of death in patients with severe burns. To date, there is no generally accepted method for preventing such complications in burn injury. One of the possible prevention options is selective intestinal decontamination (SID). This method is based on the enteral administration of non-absorbable antimicrobial agents. The preventive effect of SID involves inhibition of intestinal microflora translocation through the mucous membranes, inasmuch as studies demonstrate that endogenous opportunistic microorganisms are a common cause of infectious complications in various critical conditions. The SID method was originally developed in the Netherlands for patients suffering from mechanical injury. Antimicrobial drugs were selected based on their high activity in relation to the main endogenous opportunistic pathogens and minimal activity against normal intestinal microflora components. The combination of polymyxin (B or E), tobramycin, and amphotericin B with intravenous cefotaxime was chosen as the first SID regimen. Other regimens were proposed afterwards, and the application field of the method was expanded. In particular, it became the method of choice for prevention of infectious complications in patients with severe burn injury. Clinical studies demonstrate efficacy of some SID regimens for preventing infectious complications in patients with thermal injury. Concomitant administration of SID and systemic preventive antibiotics and addition of oropharyngeal decontamination increases the method efficacy. SID is generally well-tolerated, but some studies show an increased risk of diarrhea with this preventive option. In addition, SID increases the risk of developing antibiotic resistance like any other antibiotic regimens.