The goal of therapy in pediatric Hodgkin lymphoma (HL) is to maximize overall survival while minimizing the morbidity of curative therapy. Key findings from recent Children's Oncology Group (COG) trials include: (i) superior event-free survival with the addition of brentuximab vedotin (Bv) in frontline regimens for high-risk disease, (ii) successful reduction in myeloablative regimens with demonstrated safety and efficacy of Bv and checkpoint inhibitor therapy in relapsed disease, and (ii) the potential to select a population that can be salvaged after relapse without receiving a stem cell transplant. The COG HL committee will lead a National cancer Institute National Clinical Trials Network phase 3 trial to evaluate the combination of Bv/nivolumab in early-stage disease. Ongoing advances in technology and blood biomarkers are increasing the ability to deliver biologically driven, personalized treatment for HL.