Since their appearance in the armamentarium for inflammatory bowel disease (IBD) more than a decade ago, antitumor necrosis factor (TNF) inhibitors have demonstrated beneficial activity in induction and maintenance of clinical remission, mucosal healing, improvement in quality of life, and reduction in surgeries and hospitalizations. However, more than one-third of patients present primary resistance, and another one-third become resistant over time. One of the main factors associated with loss of response is the immunogenicity of anti-TNF biologics leading to the production of antidrug antibodies (ADAbs) accelerating their clearance. In this review we present the current state of the literature on the place of TNF and its blockage in the treatment of patients with IBD and discuss the usefulness of serum trough levels and ADAb monitoring in the optimization of anti-TNF therapies.