Objective To introduce the conception and pediatric use of unlicensed/off-label medicines, and explore the relationship between them and adverse drug reactions in children. Methods A number of native and international literatures involved from 2000 till now was collected, analyzed and reviewed. Results The results indicated that different children population has different characteristic. In general, off-label/unlicensed prescription rates ranged widely, and higher rates were found in hospital versus community patients, especially in neonates. The most common category of off-label use were age and dose. There was no consensus about whether off-label/unlicensed medicines would increase the risk of adverse drug reactions. Further studies are needed to evaluate it in the future. Conclusion Unlicensed and off-label medicines are widely used in pediatric patients and we should look at the issue objectively. To ensure that children are not exposed to unnecessary risks, the state shall establish rules and regulations of health care organizations and promote the development of controlled clinical trials for children’s medicines.