Perianal fistulas in Crohn's disease (CD) are a major problem. In majority of patient, inflammation involves the rectum. Perianal fistulas in CD pose a diagnostic and therapeutic challenge due to severe symptoms and worse prognosis compared to cryptogenic fistulas. The accurate diagnosis is crucial for an effective treatment of CD-related perianal fistulas, and the following should be determined: anatomy of the fistula, possible strictures and inflammation of the alimentary tract, including the rectum and the anal canal. Treatment of fistulas might be challenging and requires cooperation between the colorectal surgeon and the gastroenterologist. The combination of surgical and pharmacological therapy is more effective than surgical or pharmacological therapy alone. In conservative treatment, aminosalicylates or steroids have little significance. In everyday practice, antibacterial chemotherapeutics, antibiotics and thiopurines are applied. The most effective are TNF-neutralizing antibodies, i.e. infliximab (IFX), adalimumab (ADA) and certolizumab (CER). Surgical management can be urgent including drainage. Elective procedures include dissection of the fistula (simple fistula) or more complex interventions such as mucosal flap or ligation of the intersphincteric portion of the fistula. Surgical interventions can be enhanced using the video-assisted anal fistula treatment (VAAFT) or negative-pressure therapy. In extreme cases, creation of a stoma may be necessary. Also, tissue glues or so-called plugs may be applied in managing perianal fistulas. The use of stem cells seems promising, i.e. application of multipotent non-hematopoietic stem cells around the fistula in order to induce immunomodulation and wound healing.