Once thought to be a relatively untreatable disease, pancreatic cancer has recently become a focus of intense clinical research. The systemic administration of gemcitabine (Gemzar) is currently considered the standard first-line treatment for patients with advanced disease. While treatment with gemcitabine has been shown to result in both clinical benefit and prolongation of survival, objective tumor responses are relatively uncommon and median survival times remain short. Several recent efforts have therefore focused on evaluating chemotherapy regimens in which gemcitabine is combined with other cytotoxic drugs. While randomized trials have now confirmed that such combinations are associated with higher response rates, they have not yet clearly demonstrated that combination therapy results in a survival advantage. Increasingly, attention has turned to a number of novel chemotherapeutic and biologic agents that appear promising and are likely to play an important future role in the treatment of patients with this disease.