The natural course of Crohn's disease is characterized by the progression from primarily inflammatory disease to a complicated stricturing or penetrating disease. This irreversible complications lead to repeated surgery and considerable disability. It may therefore be argued that a window of opportunity for intensive treatment exists early in the disease course. Healing of the mucosa has been shown to be a strong predictor of improved outcome of Crohn's disease on the long-term, in terms disease control, hospitalizations, and surgery. Anti-tumor necrosis factor (TNF)-alpha therapy has shown to be a strong inducer of mucosal healing and it may be argued that early treatment with anti-TNF's and/or immunomodulators may be the preferable approach in selected patients. The main concern with such strategies is safety, especially the risk of lymphoma's and infections. This paper aims to review the existing data regarding the benefits and disadvantages of inverting the classic step up therapeutic paradigm.