Despite the many advances in oncology over the last few decades, almost all patients with pancreatic cancer eventually die of the disease. Recent advances, however, have led to the development of more effective therapies. In pancreatic cancer, as in many other malignancies, significant progress in the understanding of important molecular processes associated with the development and progression of the disease is helping tailor more effective treatment strategies. Molecularly targeted agents are offering hope for their potential role in helping translate the improved activity of combination chemotherapy into improved survival. This article summarizes the data from studies that established standards of care and others that created controversy, and reviews novel treatment strategies for this intractable disease.