This CEC Oncology ONS Chapters Series is targeted to oncology nurses and advanced nurse practitioners serving as part of an interprofessional healthcare team providing care for pediatric and adult patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). To introduce this session, learners will first understand the rationale for using asparaginase, both in ALL/LBL and in other disease states. Following this, a discussion of clinical trial data supporting asparaginase-containing regimens along with relevant product-distinguishing information will highlight must-know information for involved oncology nurses. In conclusion, the focus will shift toward toxicities associated with asparaginase use and the differences among infusion reactions and hypersensitivity reactions that can make routine use of and adherence to these therapies challenging in real-world settings. An interactive case-based approach will then serve to solidify these important concepts and integrate newly acquired practical information.