With the development of highly efficient sequencing techniques and the expected more diffuse availability of patient specific genotyping data, particularly for severe life threatening disease such as pediatric ALL, thiopurines pharmacogenetics may significantly contribute to reduce adverse effects and improve efficacy, by considering multilocus genotyping of TPMT and NUDT15. More research is needed to further improve pharmacogenetics of thiopurines by including additional gene variants, such as ITPA and PACSIN2, to obtain further clinical and mechanistic evidence. This evidence concerns the gene ITPA and acute lymphoblastic leukemia.