Background: Despite intensive diagnostic testing, a septic focus might prove difficult to detect in intensive care unit (ICU) patients. Yet it is essential to identify the source of infection in order to consider all source control options. An advanced diagnostic procedure to establish the septic focus is a positron emission tomography / computed tomography (FDG-PET/CT) scan. The purpose of this review is to explore the diagnostic value of FDG-PET/CT in ICU patients. Methods: A systematic search was performed to identify all relevant evidence. Titles and abstracts were screened using predefined criteria. Results: Ten articles were included. No major multicentre prospective studies are available. The current evidence shows results with sensitivities between 85% and 100% and a specificity between 50% and 79% in finding a focus of infection. A change of therapy due to the results of a FDG-PET/CT scan is reported in 15-71% of all cases. Conclusion: FDG-PET/CT could be a helpful examination to determine the focus in sepsis of unknown origin. However, several pitfalls and precautions should be taken into consideration. © 2019, Netherlands Society of Intensive Care. All rights reserved.