There has been a continual evolution of therapy for Crohn’s disease (CD) over the past decade since the introduction of biological therapies targeting tumor necrosis factor-α. Conventional agents continue to be safe and effective for patients with mild to moderately active CD and, in population series, less than half of the patients with CD require corticosteroid therapy. In contrast, patients presenting at young ages, those with extensive disease, deep ulcerations, transmural complications or extraintestinal complications that require corticosteroid therapy have a poor prognosis. Introduction of immunosuppressives late in the course or for patients with steroid-dependent or steroid-refractory disease have not changed the ‘natural history’ of CD or the need for eventual surgical resections. There is increasing evidence that early intervention with immunosuppressives or biologic agents at the same time as corticosteroids, or biologic agents targeting tumor necrosis factor or adhesion molecules, can have rapid and prolonged benefits, including steroid sparing, reductions in hospitalizations and, perhaps, reductions in the need for surgery. Treatment should be optimized according to the patient status and response with whichever level of therapy is introduced and maintained.