Gastrointestinal failure is a polymorphic syndrome with multiple causes. Managing the different situations from a practical, metabolic, and nutritional point of view is challenging, which the present review will try to address. Acute gastrointestinal injury (AGI) has been defined and has evolved into a concept of gastrointestinal dysfunction score (GIDS) built on the model of Sequential Organ Failure Assessment (SOFA) score, and ranging from 0 (no risk) to 4 (life threatening). But there is yet no specific, reliable and reproducible, biomarker linked to it. Evaluating the risk with the Nutrition Risk Screening (NRS) score is the first step whenever addressing nutrition therapy. Depending on the severity of the gastrointestinal failure and its clinical manifestations, nutritional management needs to be individualized but always including prevention of undernutrition and dehydration, and administration of target essential micronutrients. The use of fibers in enteral feeding solutions has gained acceptance and is even recommended based on microbiome findings. Parenteral nutrition whether alone or combined to enteral feeding is indicated whenever the intestine is unable to process the needs. The heterogeneity of gastrointestinal insufficiency precludes a uniform nutritional management of all critically ill patients but justifies its early detection and the implementation of individualized care.