Pancolitis affects approximately 20% to 40% of the total ulcerative colitis population and remains a therapeutic challenge for clinicians. Practitioners must focus on pancolitis when evaluating a patient for ulcerative colitis, because pancolitis is associated with more severe and fulminant disease and a higher rate of colorectal cancer and colectomy. It is imperative for clinicians to be knowledgeable in the clinical course, medications, and appropriate manner to induce and maintain clinical remission to prevent serious sequelae of the disease. The purpose of this article is to provide a review of the treatment of pancolitis for general gastroenterologists, because medical management decisions have life-long effects for this subgroup of patients.