L-asparaginase (L-Aspa) is utilized as a part of the therapy in children with acute lymphoblastic leukemia (ALL), achieving remission in 83–95% of the younger patients. Hypersensitivity reactions, as well as liver and pancreatic cytotoxicity, are severe documented side effects. L-Aspa-induced acute pancreatitis (AP) has been observed in 2.5–16% of treated patients. Patients with mild pancreatitis may be retreated with L-Aspa if they have no clinical symptoms within 48 hours, amylase and lipase levels are less than three times the normal’s upper limit, and there is no evidence of pseudocysts or necrosis on imaging. It is crucial to monitor patients under L-Aspa therapy, through careful observation of clinical signs and laboratory follow-up, as well as a continuous checkup for associated medications.