Immunotherapy has become the “fourth pillar” of cancer treatment, after chemotherapy, radiation therapy, and surgery. With outcomes for several metastatic or recurrent cancers, including neuroblastoma and osteosarcoma, reaching plateaus in recent years, immunotherapeutic agents are increasingly being looked to in the most challenging treatment situations. The pediatric surgeon will come into contact with immunotherapy agents likely in two circumstances: while performing ancillary procedures (such as central line placement, chest tubes, or abscess drainages) for patients on immunotherapeutic agents or while performing primary resection of a tumor for a patient whose treatment plan includes immunotherapy (such as in neuroblastoma). A familiarity with the primary concepts of immunotherapy and the main classes of agents is therefore required. This chapter will provide a brief overview of the main types of agents the pediatric surgeon is likely to encounter. We will then discuss their application to two of the most common pediatric solid tumors, neuroblastoma and osteosarcoma. Finally, we briefly explore preclinical efforts to overcome challenges particular to the application of immunotherapeutics in pediatric solid tumors.