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Any drug can potentially induce a hypersensitivity reaction. If after the allergological work‐up the drug hypersensitivity reaction is confirmed, in most cases, the simple avoidance of the culprit drug and a suggestion of an unrelated alternative is enough. However, there are circumstances where the choice to stop the treatment affects the survival, the safety and/or the quality of life of the patient and the global outcome of the disease in question. When this occurs, drug desensitization can be the answer and should not be viewed as an extravagance, nor the pediatric age should be considered a contraindication. Drug desensitization in children can be safely and successfully performed, having a positive impact on the survival and overall prognosis. In general, the indications for DDS are the same in adults as in children. However, in this age group there are specificities that this paper aimed to describe, reviewing the mechanisms behind drug hypersensitivity and rapid drug desensitization, types of protocols, indications, and contraindications, as well as several technical aspects that are specific to the pediatric age. [ABSTRACT FROM AUTHOR]