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Personalized medicine is focused on research disciplines that contribute to the individualization of therapy, such as pharmacogenomics and pharmacotranscriptomics. Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. It is one of the pediatric malignancies with the highest cure rate, but still a lethal outcome due to therapy accounts for 1–3% of deaths. Further improvement of treatment protocols is needed through the implementation of pharmacogenomics and pharmacotranscriptomics. The research study was aimed at discovering pharmacogenetic and pharmacotranscriptomic markers of response to therapy with thiopurine and glucocorticoid drugs, methotrexate and vincristine in children with ALL in Serbia. Blood and bone marrow samples from children with ALL were collected at the University Children's Hospital in Belgrade. Variants in the studied genes were detected by PCR and Sanger sequencing. The expression level of NUDT15 in mononuclear cells was determined by real-time PCR. Next-generation sequencing using cancer panel TruSeq Amplicon, Illumina was also performed to assess drug resistance. Correlation of pharmacomarkers with clinical parameters was performed using statistical tests. A polygenic risk score based prediction model for the development of methotrexate-induced hepatotoxicity was developed. A number of molecular markers responsible for the efficacy, side effects and toxicity of drugs used to treat ALL, ie. glucocorticoids, vincristine, asparaginase, anthracyclines, thiopurines and methotrexate. Their application in clinical practice is still insufficient. Research efforts should be focused on analyzing data and designing predictive models that use machine learning algorithms. Bioinformatics tools and the implementation of artificial intelligence will help personalized medicine come to life in clinical practice. [ABSTRACT FROM AUTHOR]