Thiopurine drugs 6-mercaptopurine (6-MP), thioguanine (TG) and azathioprine (AZA) are widely used immunosuppressive treatment in pediatric patients with inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL). However, the incidence of adverse reactions especially myelosuppression and hepatotoxicity is high. The metabolism and transformation of thiopurine drugs are mediated by thiopurine S-methyltransferase (TPMT), Nudix hydrolase 15 (NUDT15), inosine triphosphate pyrophosphohydrolase (ITPA) and multidrug resistance-associated protein (MRP4). Genetic polymorphisms in genes encoding above-mentioned drug-metabolizing enzymes and transporter proteins can significantly in?uence the pharmacokinetics and pharmacological e?ects of thiopurines and can be significant determinants of the efficacy and toxicity of therapy. There is still a gap between the current drug treatment strategy and precise clinical application of thiopurines. In this article, we review the studies of pharmacogenetics of thiopurines and therapeutic drug monitoring of active metabolitesto provide a new insight into the precise clinical application to thiopurines.