Anti-tumour necrosis factor (TNF) antibodies have been widely used for approximately 25 years now. The first clinical observations in patients with refractory Crohn's disease rapidly responding to infliximab prompted accelerated clinical development and approval for this indication. However, many questions remained unanswered when this treatment came to market related to maintenance schedules, pharmacokinetics, toxicity and positioning. Many of these open questions were addressed by investigators and sponsors during more than two decades of clinical use. The authors were among the first to use infliximab in Crohn's disease and felt that now is a good time to look back and draw lessons from the remarkable anti-TNF story. Even today, new insights continue to appear. But more importantly, what was learnt in the past 25 years has created a platform for future development of even stronger and safer therapies. We should not forget to learn from the past.