Metoclopramide, cisapride, and erythromycin are commonly administered to reduce the duration of postoperative ileus (POI). As these agents are not without potential adverse effects, their efficacy in shortening the duration of POI should be evaluated. The etiology of POI is not well understood and therefore the precise treatment is unclear. Nasogastric suction is the mainstay of therapy, and management of fluid and electrolyte imbalances is crucial. The role of prokinetic agents is less understood. Available literature evaluating these drugs specifically for POI were reviewed, but results are confounded by issues such as sample size, variability in types of operations performed, and insensitive end points (flatus, bowel sounds). No literature supports reducing the duration of POI with metoclopramide, and limited data show benefit with cisapride. Data evaluating erythromycin are sparse, and the drug is believed to be ineffective. Domperidone, a prokinetic agent not available in the United States, has not been evaluated in POI. Due to these limitations, treatment remains largely supportive with a limited role for prokinetic agents.