The era of biologic agents for the treatment of Crohn's disease has brought about significant benefits for patients, and since the introduction of infliximab at the turn of the century, the entire field has moved on rapidly. Clinicians now have multiple agents at their disposal and a choice between several different anti-inflammatory mechanisms of action. This has allowed unprecedented improvements not only in symptoms and quality of life for patients previously refractory to conventional treatments but also for demonstrated healing of the intestinal mucosa and resolution of perianal fistulation. However, despite the undisputed efficacy of these agents, there remains a significant proportion of patients who fail to gain a meaningful benefit. Through years of studying infliximab and its counterpart anti-tumour necrosis factor (anti-TNF) agent, adalimumab, we now understand that strategies such as combining use with a conventional immunomodulator or measuring serum levels can help to optimise outcomes and reduce the proportion of patients for whom treatment fails. Work is ongoing to understand whether these principles apply to newer biologics such as vedolizumab and ustekinumab. In addition, novel approaches are being investigated in an attempt to maximise the benefit that these agents could offer. In this article, we summarise these new understandings and consider ways in which they could be integrated into clinical practice for the benefit of patients.