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Asparaginase is a key molecule in the treatment of acute lymphoblastic leukemia that has improved response rates to chemotherapy. However, its use has not been without consequences. Therapeutic efficacy is sometimes achieved at the expense of introducing toxicities that can lead to treatment discontinuation. For example, patients can develop hyperammonemia which can be symptomatic, leading to neurological disorders that can go as far as hyperammonemic coma or even death. Through a state-of-the-art literature review, the objective is to understand the disparity of ammonia values as well as the clinical heterogeneity for a given ammonia concentration. A literature review including more than eighty publications was conducted. The glutaminase activity of asparaginase seems to play an important role in the development of hyperammonemia. At present, no risk factors have been identified for the development of hyperammonemia. However, the question of the impact of the pre-analysis phase needs to be considered. Indeed, asparaginase continues its activity in vitro, which leads to an artificial increase in ammonia.