The arrival of biologics, in particular anti-Tumor Necrosis Facteur (TNF), at the end of the nineties, revolutionnized treatment of inflammatory bowel diseases. Concomitantly, immunosuppressants (thiopurines, methotrexate) are used more widely and earlier in the disease course. Infliximab and adalimumab are very effective in more than two-thirds of patients, including those with fistula. This efficacy is long lasting in one-third of patients. Main side-effects of anti-TNF are opportunistic infections (intracellular bacteria) which should be prevented and diagnosed early. Anti-TNF are safe in the long-term, however, there is a particular concern regarding the risk of hepatosplenic T cell lymphomas in young men receiving bitherapy with thiopurine and anti-TNF. The old strategy of adapting the therapeutic response to severity of symptoms and disease activity has no impact on natural history of the disease and should be abandoned. Most authors now favour an aggressive therapeutic approach in selected patients, before they develop irreversible anatomic lesions. This new strategy may change natural history and will become safer with a better knowledge of side-effects of immunosuppressants and biologics and how to prevent them. Moreover development of new therapeutic agents may permit to avoid surgery in patients who do not respond to therapy.