Advances in chemotherapy for pancreatic cancer have been limited. In the past decade, the standard therapy for metastatic disease has switched from 5-fluorouracil (5-FU) to gemcitabine. However, several other cytotoxic agents have shown limited but promising efficacy in pancreatic cancer, and many of these appear to be well suited for combination chemotherapy. Although 5-FU and cisplatin have not demonstrated substantial survival benefits when combined with gemcitabine, results of several phase III trials with other agents are still pending. For locally advanced disease, most recent studies have incorporated gemcitabine into combined-modality therapy. Similarly, in surgically resectable disease, current trials are incorporating gemcitabine into adjuvant therapy. Other trials are using neoadjuvant therapy as a possible means to improve upon current surgical results. However, much hope comes from the development of newer "targeted" therapies for this disease. Although matrix metalloproteinase inhibitors and farnesyl transferase inhibitors did not appear to be effective in initial studies, other targeted therapies are beginning to enter clinical trials.