The aim of this systematic review is to critically evaluate the use and effectiveness of osteopathic manipulative treatment (OMT) as an adjunct treatment option for infants in the neonatal intensive care unit (NICU). Methods: A systematic literature search was conducted through February 2016 using three databases (PubMed, Scopus, and Embase). The search was performed for any type of clinical study using OMT on infants in the NICU. Case reports, cohort studies, randomized controlled trials and basic research were included. There were no date limitations for these searches. Results: Ten titles met the criteria for this review. Results suggest a potential positive effect of osteopathic manipulation on infants admitted to the NICU in terms of decreased LOS and cost benefits. Only one study showed negative effects. Conclusion: Clinically relevant effects of OMT were found for reducing LOS and cost as well as improving functional status in infants admitted to the NICU. Only one study found OMT to cause a longer LOS.