In most intensive care units (ICUs) in the Netherlands, selective decontamination of the digestive tract (SDD) is currently a routine strategy to prevent secondary infection. The successfulness of infection prevention by SDD depends on whether decontamination is achieved or not. In addition, the rising rate of abnormal carriership with potential pathogenic and resistant microorganisms at the moment of ICU admission makes it sometimes difficult to obtain decontamination. It may be necessary to make adaptations to the standard antibiotic regime in SDD which is usually polymyxin, tobramycin and amphotericin B. Furthermore, persistent colonisation may need additional actions to enable the SDD regime to be successful. This article summarises tips and tricks to achieve successful decontamination of ICU patients, even in case of multi-resistant strains and persistent pathological carrier state. © 2019, Netherlands Society of Intensive Care. All rights reserved.