5-Aminosalicylic acid (5-ASA) is the mainstay of therapy for inflammatory bowel disease (IBD), particularly ulcerative colitis. 5-ASA is the active moiety in sulfasalazine, which was initially developed for the treatment of rheumatoid arthritis more than 60 years ago, by linking 5-ASA with sulfapyridine Because many of the side effects related to sulfasalazine were found to be due to sulfapyridine, several drugs that contain 5-ASA, and lack the side-effect profile of sulfasalazine, have been developed during the last 2 decades. These drugs have proven to be quite effective in treating mild-to-moderate symptoms of IBD, as well as inducing and maintaining remission. Although they exert anti-inflammatory effects, their exact mechanism of action remains elusive. Nonetheless, their success in treating IBD has led to studies using this class of drugs for novel indications. Several recent studies have evaluated the use of 5-ASA drugs (mesalamine) for the treatment of uncomplicated acute diverticulitis. In this review, we will briefly discuss the development of 5-ASA releasing drugs, their metabolism, side effects, indications, mechanisms of action, and the rationale for the clinical use of mesalamine in colonic diverticulitis.