The concept of a 'step-up' or 'top-down' approach to the treatment of Crohn's disease has evolved from the impact of novel anti-TNF (anti-tumour necrosis factor) therapies that have been effective for patients who are refractory to other medical treatments. In addition, the potential to produce mucosal healing with anti-TNF treatments without the well-recognized systemic complications of glucocorticoid therapy has created debate as to whether earlier, more aggressive, therapies should be advocated. This controversy arises at a time when the concept of sequential therapy to induce and maintain remissions for Crohn's disease has begun to be accepted and precedes our ability to define the concept of disease modification or predict the natural history of Crohn's disease based upon clinical, pathological, molecular orgenetic criteria. Evidence for therapeutic efficacy in Crohn's disease is presented as a prologue to considerations necessary to determine the benefits and risks of early aggressive treatment versus sequential approaches based upon disease severity.