Progress in the management of adenocarcinoma of the pancreas has clearly been documented in recent years. Surgical outcomes have improved dramatically, and the preponderance of data from randomized clinical trials affirm that adjuvant therapy, in the form of combination chemoradiotherapy, improves outcomes over surgery alone in patients with resected disease. Newer chemotherapeutic agents such as gemcitabine have led to significant improvements over 5-fluorouracil alone, and patients have benefited from improved methods of delivering conformal radiotherapy. As the clinical benefits of postoperative adjuvant therapy become increasingly evident, researchers have begun to explore the utility of including preoperative or "neoadjuvant" regimens to standard 5-fluorouracil-based chemoradiotherapy. Initial results with this strategy are promising, and will likely influence the direction of future research. A growing understanding of the molecular biology of the disease has opened doors to rich new areas of research, and targeted therapies will likely play an important role in newly developing treatment paradigms. Just cause for optimism exists, but much work remains to be done. New adjuvant therapies need to be developed and tested, in carefully designed, well-executed, efficient clinical trials.