Pancreatic cancer is refractory to most chemotherapy. For many years, the only active agent for this disease was gemcitabine, which has very modest activity. Two new regimens, gemcitabine plus erlotinib and gemcitabine plus capecitabine, have recently demonstrated statistically significant survival improvements compared with single-agent gemcitabine. Several key negative studies have also been reported recently. This review discusses recent trials that have changed the standard of care for patients with advanced pancreatic cancer.