The introduction of biologic agents and particularly of anti-tumor necrosis factor antibodies dramatically changed the therapeutic algorithm in patients with inflammatory bowel diseases. Although the efficacy of these agents has been demonstrated clearly, optimal treatment strategies are debated. Recent trials advocate the introduction of biologic agents at an early stage to prevent debilitating complications. However, significant adverse events have led to careful selection of patients who will benefit most from long-term treatment with biologic agents. Once on biologic therapy, scheduled maintenance therapy is recommended to minimize the risk of loss of response. Nevertheless, treatment adaptation is frequently necessary in patients who lose response. Interventions encompass strategies to increase drug exposure by increasing the dose or decreasing the dosing interval, or by changing to another biologic agent. Finally, it remains unclear if and when a biologic agent can be stopped in patients with long-standing remission.