In the last decade, biologic agents, in particular infliximab and adalimum-ab, have deeply changed the therapeutic armamentarium of inflammatory bowel disease (IBD). However, these drugs have a number of contraindications and side-effects that physicians should know so to avoid and eventually manage them. Another important issue is the early introduction of immunomodulators and biologics in the therapeutic algorithm of IBD, the so called "top-down" approach compared to the traditional "step-up" approach. In this review, the indications to the use of anti-TNF-alpha molecules in IBD are briefly reported and the potential benefits and disadvantages of a more aggressive approach are discussed.