Induction and maintenance of remission, mucosal healing, the avoidance of surgical intervention, and decreasing the likelihood of cancer developing are the primary therapeutic goals in ulcerative colitis (UC). For the traditional therapies, 5-aminosalicylic acid (including mesalamine), corticosteroids, and thiopurines (azathioprine and mercaptopurine), there are major changes evolving in terms of formulation, patterns of use, and appreciation of long-term benefits and toxicities. The calcineurin inhibitors cyclosporin and tacrolimus, and infliximab, have recently defined, well-established roles. Preliminary supportive evidence is emerging in relation to novel antiinflammatory molecules such as curcumin, manipulation of the bacterial flora, enhancement of the mucosal barrier, and direct epithelial restoration. For patients in whom the disease is resistant to standard simple therapies, strategies are required to integrate these developing and new therapies into clinical practice. This review aims to highlight the evidence supporting new patterns of use of existing therapies and new therapies, and to devise therapeutic pathways that incorporate these new treatments. We propose how treatment might be optimized to improve the outcome in patients with mild-to-moderately active UC, chronic active UC, resistant proctitis, and fulminant UC.