Thiopurines and biologics are being used earlier and more frequently for the treatment of Crohn's disease and ulcerative colitis. These medications are generally well tolerated and usually do not require cessation due to a side effect. Rare but serious infections and cancers may develop in patients on these immunosuppressants. Evidence-based data are lacking to guide physicians on whether continuing or stopping thiopurines and biologics is necessary and, when a side effect does occur, if and when restarting these medications is feasible. The aim of this review was to outline the infectious and malignant complications that may develop on these treatments and to provide recommendations for continuing, stopping, and restarting thiopurines and biologics once a patient develops a treatment-related complication. These are not formal guidelines and should not replace individualized care by the treating physician.