This article reviews the role of corticosteroids, sulfasalazine and mesalazine (5-aminosalicylic acid, mesalamine), immunosuppressive agents and alternative novel drugs for the treatment of distal ulcerative colitis. Short cycles of traditional, rectally administered corticosteroids (methylprednisolone, betamethasone, hydrocortisone) are effective for the treatment of mild to moderately active distal ulcerative colitis. In this context, their systemic administration is limited to patients who are refractory to either oral 5-amino-salicylates, topical mesalazine or topical corticosteroids. Of no value in maintaining remission, the long term use of either or topical corticosteroids may be hazardous. A new class of topically acting corticosteroids [budesonide, fluticasone, beclomethasone dipropionate, prednisolone-21-methasulphobenzoate, tixocortol (tixocortol pivalate)] represents a valid alternative for the treatment of active ulcerative colitis, and may be useful in the treatment of refractory distal ulcerative colitis. Although there is controversy concerning dosage or duration of therapy, oral and topical mesalazine is effective in the treatment of mild to moderately active distal ulcerative colitis. Sulfasalazine and mesalazine remain the first-choice drugs for the maintenance therapy of distal ulcerative colitis. Evidence exists showing a trend to a higher remission rate with higher doses of oral mesalazine. Topical mesalazine (suppositories or enemas) also is effective in maintenance treatment. For patients with chronically active or corticosteroid-dependent disease, azathioprine and mercaptopurine are effective in reducing either the need for corticosteroids or clinical relapses. Moreover, they are effective for long term maintenance remission. Cyclosporin may be useful in inducing remission in patients with acutely severe disease who do not achieve remission with an intensive intravenous regimen. Existing data suggest that azathioprine and mercaptopurine may be effective in prolonging remission in these patients. The role of alternative drugs for the treatment of distal ulcerative colitis and its different forms is reviewed. In particular data are reported concerning the effectiveness of 5-lipoxygenase inhibitors, topical use of short chain fatty acids, nicotine, local anaesthetics, bismuth subsalicylate enema, sucralfate, clonidine, free radical scavengers, heparin and hydroxychloroquine.