Metastatic pancreatic cancer is one of the leading causes of cancer-related death in North America and Europe. The high mortality rate associated with pancreatic cancer is related to the fact that the vast majority of patients develop incurable, metastatic disease. Such patients have, in the past, had few treatment options. In recent years, however, the systemic administration of gemcitabine has been accepted as a standard first-line treatment for patients with advanced pancreatic cancer. While treatment with gemcitabine has been shown to result in both clinical benefit and in prolongation of survival, objective tumour responses following therapy with gemcitabine are relatively uncommon and median survival times remain short. Current efforts have, therefore, focused on evaluating chemotherapy regimens in which gemcitabine is combined with a second cytotoxic agent. Several such combinations appear to be associated with higher objective response rates than single-agent gemcitabine and have been well-tolerated in early clinical trials. Ongoing, prospectively randomised clinical trials will help better define the efficacy of these new combinations and will determine if they result in a significant benefit when compared to gemcitabine monotherapy. A number of novel chemotherapeutic and biological agents also appear promising and are likely to play a future role in the treatment of patients with advanced pancreatic cancer.