Malignant primary brain tumors are the most common cancer in children aged 0–14 years, and are the most common cause of death among pediatric cancer patients. Compared to other cancers, pediatric brain tumors have been difficult to diagnose and study given the high risk of intracranial biopsy penetrating through vital midline structures, where the majority of pediatric brain tumors originate (Ostrom et al., 2015). Furthermore, the vast majority of these tumors recur. With limitations in the ability to monitor using clinical and radiographic methods alone, minimally invasive methods such as liquid biopsy will be crucial to our understanding and treatment. Liquid biopsy of blood, urine, and cerebrospinal fluid (CSF) can be used to sample cfDNA, ctDNA, RNA, extracellular vesicles, and tumor-associated proteins. In the past year, four seminal papers have made significant advances in the use of liquid biopsy in pediatric brain tumor patients (Liu et al., 2021; Cantor et al., 2022; Miller et al., 2022; Pagès et al., 2022). In this review, we integrate the results of these studies and others to discuss how the newest technologies in liquid biopsy are being developed for molecular diagnosis and treatment response in pediatric brain tumors.