The incidence of inflammatory bowel diseases (IBD) is rising worldwide. The therapeutic options for IBD are expanding, and the number of drugs with new targets will rapidly increase in coming years. A rapid step-up approach with close monitoring of intestinal inflammation is extensively used. The fear of side effects represents one the most limiting factor of their use. Despite a widespread use for years, drug induced liver injury (DILI) management remains a challenging situation with Azathioprine and Methotrexate. DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies. The aim of this review is to report incidence, physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.