Go online to PeerView.com/JFN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Optimized use of asparaginase is a cornerstone of successful administration of multiagent chemotherapy in acute lymphoblastic leukemia (ALL) and has implications for patient outcomes across populations—are you prepared for the emergence of novel asparaginase formulations and the use of strategies that can help avoid treatment discontinuation? This MasterClass & Case Forum video presents an opportunity to understand and surmount the challenges associated with delivering effective ALL care with the asparaginase component of modern therapy. In this activity, an expert panel addresses topics ranging from current guidance on first- and second-line asparaginase options, monitoring and management of barriers such as asparaginase hypersensitivity, and therapeutic planning using available tools to maintain asparaginase exposure. Upon completion of this activity, participants should be better able to: Summarize comprehensive management recommendations for pediatric, AYA, and adult patients with ALL, including chemotherapy and asparaginase protocols, immunotherapy, and tyrosine kinase inhibitors; Cite the clinical impact of E coli asparaginase hypersensitivity and asparaginase discontinuation in ALL, including in pediatric, AYA, and adult populations; Develop evidence-based treatment plans for asparaginase sequencing with E coli and Erwinia asparaginase, including recombinant formulations; and Manage E coli asparaginase hypersensitivity, including monitoring and strategies for switching to Erwinia asparaginase options.