The past few years have seen increased knowledge and optimism on the use of biological therapy in Crohn's disease. Important lessons have been learned from the expanding clinical experience with infliximab, fuelling belief that current treatment will continue to evolve as therapy is aimed at specific targets within the immune cascade. Several other studies of agents that target tumour necrosis factor-alpha revealed mixed and sometimes disappointing results. However, this was balanced by encouraging results with agents that inhibit lymphocyte trafficking, as well as with other biological agents. Previous disappointing results of biological therapy in ulcerative colitis have been overcome with recent positive clinical trials with infliximab and the anti-CD3 antibody visilizumab. There now appears to be an expanding array of treatment options available to clinicians; however, as the number of potential molecular targets expands, unanswered questions remain regarding optimal treatment strategies, the long-term safety of biologicals and the ability of these novel and often expensive therapies to alter the natural history of the disease.