Background: Cyclic (discontinuous) infusion of parenteral nutrition (PN) presents a clear practical advantage over continuous 24‐hour infusion in patients receiving long‐term or home PN. It is important for nutrition support clinicians to recognize the metabolic consequences of cyclic infusion. Methods: A literature search was conducted through PubMed (1948 to December 2009) and MEDLINE (1950 to November 2009) using the search term parenteral nutrition plus any of the following: cycling, cycle, cyclic, discontinuous, intermittent, bolus. Prospective clinical studies characterizing the metabolic effects of cyclic PN infusion in humans and their references were reviewed. Results: Twenty‐five studies met inclusion criteria and were included in the review. Sample sizes were 4‐65 (18 studies examined ≤20 patients, 9 examined ≤10 patients). Eight studies had important design elements that limit interpretability. Cyclic and continuous PN infusions result in similar nitrogen balance and circulating counterregulatory hormone concentrations. Following PN infusion, carbohydrate oxidation decreases, fat oxidation increases, and the respiratory quotient decreases. In acutely ill mechanically ventilated patients, carbon dioxide production increases. Cyclic infusion may stabilize liver function tests in some patients with mild hyperbilirubinemia (≤20 ng/mL) on continuous PN infusion. Abrupt infusion initiation may cause hyperglycemia. Abrupt discontinuation may cause hypoglycemia, predominantly in children younger than 2‐3 years old, which may decrease with infusion tapering. Cyclic PN infusion is not associated with increased daily calcium, phosphorus, magnesium, or vitamin D losses. Conclusions: These results indicate a favorable risk–benefit profile of cyclic PN infusion in most patients receiving long‐term or home PN, in support of current practices.