Precision oncology is a treatment strategy designed to tailor molecularly targeted agents to the genomic profile of a tumor. This approach is based on the idea that utilizing therapeutic agents with molecular mechanisms known to target the precise genetic alterations in a tumor will improve outcomes compared to traditional broad-spectrum chemoradiation strategies while decreasing off-target treatment-related toxicities. Precision medicine is well-established in adult oncology and gaining traction in pediatric oncology. Due to the significant differences in genomic alterations between childhood and adult tumors, molecularly targeted therapies exist for only a small subset of pediatric cancers. Clinically utilized molecularly targeted drugs are roughly divided into two categories: small molecule inhibitors and macromolecules, including monoclonal antibodies. Here, we review current targeted treatment strategies utilized in the management of pediatric cancers.