Sulfasalazine, olsalazine, balsalazide, delayed-release mesalamine, controlled-release mesalamine, mesalamine pellets, and Multi-Matrix System mesalamine are effective first-line therapies for the treatment of mildly to moderately active ulcerative colitis and for subsequent maintenance of remission. For induction therapy it is unclear if there is a dose response above 1.5 g, and for maintenance therapy existing data do not support a dose response above 1.5 g. Sulfasalazine has more frequent side effects than olsalazine, balsalazide, and mesalamine formulations. Once-daily dosing with multi-matrix system mesalamine 1.2 g tablets may lead to optimal compliance. Mesalamine >/= 1.2 g and sulfasalazine >/= 2 g reduce the risk of colorectal cancer in patients with ulcerative colitis. Drug formulations, efficacy expectations and dose response, toxicity expectations, compliance considerations, and chemoprevention considerations are reviewed.