In the 1990s, tumour necrosis factor-α inhibitor therapy ushered in the biologic therapy era for inflammatory bowel disease, leading to marked improvements in treatment options and patient outcomes. There are currently four tumour necrosis factor-α inhibitors approved as treatments for ulcerative colitis and/or Crohn's disease: infliximab, adalimumab, golimumab and certolizumab pegol. Despite the clear benefits of tumour necrosis factor-α inhibitors, a subset of patients with inflammatory bowel disease either do not respond, experience a loss of response after initial clinical improvement or report intolerance to anti-tumour necrosis factor-α therapy. Optimizing outcomes of these agents may be achieved through earlier intervention, the use of therapeutic drug monitoring and thoughtful switching within class. To complement these approaches, evolving predictive biomarkers may help inform and optimize clinical decision making by identifying patients who might potentially benefit from an alternative treatment strategy. This review will focus on the current use of tumour necrosis factor-α inhibitors in inflammatory bowel disease and the application of personalized medicine to improve future outcomes for all patients.