Functional gastrointestinal dysmotility is a common condition that affects premature infants. Delay in achievement of full enteral nutrition results in dependence on prolonged parenteral nutrition, predisposing to adverse outcomes. Studies in recent years show apparently conflicting results regarding the use of prokinetic agents in preterm infants. This review aims to evaluate these studies to determine whether use of these agents in premature infants is beneficial and justified.Randomized controlled trials in recent years have been performed to investigate the effectiveness of erythromycin in the treatment of nonobstructive gastrointestinal dysmotility in preterm infants. Overall, neither low-dose regimes nor prophylactic trials have been shown to be useful. High-dose regimes used as rescue therapy of infants with established gastrointestinal dysmotility have consistently shown clinical benefit. Theoretical risks of prolonged antibiotic use, such as emergence of antibiotic resistance and abnormal intestinal microbiota, have not been fully evaluated.Judicious use of high-dose erythromycin in premature infants as rescue therapy is probably justifiable. Further research in this area is warranted to develop newer prokinetic agents which may improve the safety profile of therapy.