Thiopurine-derivates azathioprine and mercaptopurine are frequently used to maintain remission in inflammatory bowel diseases (IBD). Despite their efficacy, more than 50% of patients discontinue therapy, mainly due to the development of adverse events. Thioguanine is an alternative thiopurine and has been conditionally licensed in The Netherlands as IBD treatment for patients after conventional thiopurine therapy failure. In this review we will provide practical information on initiating and maintaining thioguanine therapy in IBD and provide information concerning safety issues and future perspectives. The thioguanine toxicity profile is relatively mild and the reported incidence of nodular regenerative hyperplasia related to thioguanine use seems comparable to conventional thiopurines and the background incidence in IBD patients. Routine monitoring of laboratory parameters and adverse events is recommended, comparable to the monitoring of patients on conventional thiopurine therapy.