Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for the majority of patients with medically refractory ulcerative colitis (UC) or UC with dysplasia, or familial adenomatous polyposis. Various forms of pouchitis frequently occur after surgery. In fact, pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. The etiology and pathogenesis of pouchitis are not entirely clear. It is generally believed that the initiation and development of the disease process of pouchitis is associated with dysbiosis of pouch reservoir, as evidenced by a favorable response to antibiotic therapy. However, the majority of the patients do not show identifiable etiopathogenetic or triggering factors, therefore being labeled to have idiopathic pouchitis. In contrast, a subgroup of patients, particularly those with antibiotic-refractory pouchitis, may have obvious triggering factors for disease flare-up and progression and may be considered to have secondary pouchitis. Therefore, pouchitis can be classified on the basis of etiology into idiopathic and secondary causes. Approximately 20-30% of patients who present with chronic pouchitis have secondary identifiable and triggering factors, including cytomegalovirus or Clostridium difficile infection, ischemia, concurrent immune-mediated disorders, radiation, collagen deposition, and use of nonsteroidal anti-inflammatory drugs. Careful evaluation of these secondary causes of pouchitis that may contribute to resistance to antibiotics should be performed before the introduction of next-line medical therapy.