The past few years have witnessed rapid developments in viral-mediated gene replacement therapy (GRT) for pediatric central nervous system (CNS) neurogenetic disorders. Here, we provide practicing pediatric neurologists with an up-to-date, comprehensive overview of these developments and note emerging trends for future research. This review presents the different types of viral vectors used in viral-mediated GRT, the fundamental properties of viral-mediated GRT, the challenges associated with the use of this therapy in the CNS, the pathway for therapy development, from translational basic science studies to clinical trials, and an overview of the therapies that have reached clinical trials in patients. Current viral platforms under investigation include adenovirus vectors (Ad), adeno-associated virus vectors (AAV), lentiviral/retroviral vectors (LVs/RVs), and herpes simplex virus type 1 (HSV-1) vectors. This review also presents an in-depth analysis of numerous studies that investigated these viral platforms in cultured cells and in transgenic animal models for pediatric neurogenetic disorders. Viral vectors have been applied to clinical trials for many different pediatric neurogenetic disorders, including Canavan disease, metachromatic leukodystrophy, neuronal ceroid lipofuscinosis, mucopolysaccharidosis III, spinal muscular atrophy (SMA), and Aromatic L-amino acid decarboxylase deficiency. Of these diseases, only SMA has a viral-mediated GRT therapy approved for marketing. Despite significant progress in therapy development, many challenges still exist. Surmounting these challenges is critical to advancing the current status of viral-mediated GRT for pediatric CNS neurogenetic disorders.