PURPOSE OF REVIEW: In this era of increasing antimicrobial resistance, use of probiotics in infection prevention has brought new perspective. However, in 2008 the, until then considered, safe use of probiotics became an important topic after publication of a trial showing excess mortality in patients on probiotic prophylaxis. In this article, we review the concept of infection prevention by probiotics and the present knowledge of the efficacy of probiotics in prevention of infections among patients with abdominal diseases and in intensive care. Safety issues of probiotics will be discussed extensively. RECENT FINDINGS: Over 30 clinical trials with probiotics to prevent infections have been published, some of which were prematurely stopped recently. Studies with critically ill patients and patients with abdominal diseases showed conflicting results regarding the effects of probiotics on infection rates, as did meta-analyses. These studies are difficult to compare because different probiotics were used which all have different efficacy and safety profiles. SUMMARY: The efficacy of probiotics in infection prevention among critically ill patients is still not unequivocally determined. The safety profile differs per probiotic strain and should not be generalized towards other strains and patient populations. A well designed and well powered clinical trial with clear endpoints to demonstrate efficacy is warranted.