The disease course of Crohn's disease (CD) can be highly heterogeneous, leading to stricturing or perforating complications and surgery in the majority of patients. Evidence is accumulating about the lack of efficacy of azathioprine (AZA) started early in the disease course for achieving steroid-free remission. Novel information, however, indicates that long-term treatment targets addressing structural damage, such as delay of disease progression or avoidance of surgery, can be achieved by early and prolonged use of AZA with or without anti-tumor necrosis factor therapy. It is hence worth reconsidering the treat-to-target strategy of immunosuppressant and immunomodulatory therapy in CD.