L-asparaginase is one of the most important agent used in multidrug chemotherapy regimens in the treatment of malignancies which derive from lymphoid system (acute lymhoblastic leukemias and non-hodgkin lymphoma). L-asparaginase leads to enzymatic cleavage of L-asparagine (amino acid essential for lymphoblasts' growth) to ammonia and L-aspartic acid, what results in depletion of L-asparagine in a serum and cerebrospinal fluid, and finally leads to destruction of lymphoblasts, which lack ability of endogenic L-asparagine production. In the course of L-asparaginase therapy severe side effects could be observed such as: coagulation disturbances, acute pancreatitis, anaphilactic shock and other types of allergic reaction, as well as liver and CNS failure. Monitoring of L-asparaginase activity in serum is recomended in order to optimalize therapy with L-asparaginase and reducing risk of severe side effects. Continuous assessment of L-asparaginase activity during therapy gives also opportunity to detect asymptomatic inactivation of L-ASPA - so called "silent inactivation", which is cused by production of antibodies against xenogenic protein, especcialy in IgG class. This process leads to shortening of half-life of L-ASPA. The paper shows presently available monitoring methods during therapy with L-ASPA, with all their pros and cons.