Current guidelines on the medical therapy of Crohn's disease recommend a step-up strategy consisting of a progressive intensification of treatment as the disease severity increases. In the last fifteen years, the introduction of biologic therapies, particularly anti-TNFα antibodies, has offered new therapeutic opportunities. The efficacy of anti-TNF-alpha therapy for inducing and maintaining clinical response or remission in moderate to severe Crohn's disease has been extensively evaluated in randomised controlled trials and meta-analyses. Moreover, anti-TNF-alpha therapy can induce mucosal healing and this property may be potentially disease-modifying. Consequently, an early introduction of biologics and/or immunomodulators (top-down strategy) in newly diagnosed Crohn's disease has been advocated. This paper will review the evidence in favour and against this approach to Crohn's disease therapy, discuss which patients are potential candidates to early aggressive treatment, and how a conventional step-up approach can be optimized. The conclusion is that an indiscriminate top-down approach does not seem to be appropriate for all patients with moderate to severe Crohn's disease.