Perianal fistulas are a major problem of patients with Crohn's disease (CD), and occur in up to 40 % of patients. The treatment of fistulizing perianal CD has recently largely evolved as a result of improvements of pharmacological and surgical approaches and the introduction of anti-TNF treatment. Especially the use of anti-TNF agents in complex or refractory perianal fistulas has been proven as the most effective medical treatment of this difficult to treat disease. Infliximab and adalimumab are the two currently available anti-TNF agents that both have shown significant efficacy in the treatment and sustained remission of perianal fistulizing CD with comparable fistula closure rates. However, despite this treatment a large number of patients have continuous disease activity and high relapsing rates whereas only a small percentage of them have a complete fistula healing. Therefore the optimal outcome is still dependent on a multidisciplinary approach with a close interaction between gastroenterologists and surgeons. The individualised treatment based on anti-TNF agents with the rational combination of antibiotic use, surgery and immunosuppressive therapy is, currently, the suggested treatment in order to achieve remission of a persistent perianal fistula. Large randomised studies are required for the long-term evaluation of the efficacy in modifying the disease course of this combined approach.