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Outcomes for children with high-grade gliomas (HGG) remain dismal despite aggressive treatment strategies. The use of targeted therapy for BRAF V600E mutated malignancies including HGG is being explored as a potentially well tolerated and effective therapeutic option. The results of adult melanoma studies demonstrating that combination therapy with BRAF inhibitors and MEK inhibitors results in prolonged survival led us to employ this treatment strategy in children with BRAF V600E mutated HGG. In this case series, we describe three pediatric patients with HGG with confirmed BRAF V600E mutation who demonstrated responses to combination therapy with dabrafenib and trametinib.