Chronic diseases are the major cause of morbidity and mortality worldwide and have shown increasing incidence rates among children in the last decades. Chronic illnesses in the pediatric population, even if well managed, affect social, psychological, and physical development and often limit education and active participation and increase the risk for health complications. The significant pediatric morbidity and mortality rates caused by chronic illnesses call for serious efforts toward better understanding of the pathogenesis of these disorders. Recent studies have shown the involvement of microRNAs (miRNAs) in various aspects of major pediatric chronic non-neoplastic diseases. This review focuses on the role of miRNAs in four major pediatric chronic diseases including bronchial asthma, diabetes mellitus, epilepsy and cystic fibrosis. We intend to emphasize the importance of miRNA-based research in combating these major disorders, as we believe this approach will result in novel therapies to aid securing normal development and to prevent disabilities in the pediatric population.