Gastrointestinal dysmotility is commonly noted in the intensive care unit and postoperative settings. Characterized by delayed passage of stool and flatus, nausea, vomiting, and abdominal distention, the condition is associated with nutritional deficiencies, risk of aspiration, and considerable allocation of health care resources. Knowledge of gastrointestinal function in health and illness continues to expand. While the factors that precipitate ileus differ between postoperative and critically ill patients, the two clinical scenarios seem to have similar mechanisms and share many of the same pathophysiologic patterns. By reviewing and comparing the literature on the respective mechanisms and contributing factors generated in these separate clinical settings, a common more comprehensive management strategy may be derived with the potential for newer innovative therapeutic options.