Azathioprine (AZA) and 6-mercaptopurine (6-MP) have been used for many years in the treatment of inflammatory bowel diseases (IBD). AZA is a prodrug that is metabolized to 6-MP, which in turn is metabolized to several metabolites including 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). The most important enzyme responsible for metabolism of purine analogues is thiopurine methyltransferase (TPMT), which activity has direct or indirect influence on serum levels of 6-MMP and 6-TG. Detection of low or absent TPMT enzymatic activity before introducing therapy with AZA or 6-MP helps to avoid potentially life-threatening post-medicament toxicity. In this review the current knowledge of rational dosage and monitoring of therapeutic effects of AZA and 6-MP in patients with IBD based on understanding of their pharmacodynamics have been presented.