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Background: MiRNAs are a class of small non-coding RNAs that are involved in the post-transcriptional regulation of gene expression. MiRNAs are considered a class of epigenetic biomarkers. These biomarkers can investigate disease at different stages: diagnosis, therapy or clinical follow-up. Objective: The aim of this paper is to highlight the innovative use of miRNAs in several childhood diseases. Methods: We conducted a literature review to search the usage of miRNAs in pediatric clinical routine or experimental trials. Results: We found a possible key role of miRNAs in different pediatric illnesses (metabolic alterations, coagulation defects, cancer). Conclusion: The modest literature production denotes that further investigation is needed to assess and validate the promising role of miRNAs as non-invasive biomarkers in pediatric disorders.