Despite advances in therapy, the average survival rate at 5 years for any patient diagnosed with pancreatic cancer remains only 6%. Throughout the course of cancer, most patients suffer a significant symptom burden and will need numerous interventions targeting these concerns. This paper highlights the most significant problems faced when caring for patients with advanced pancreatic cancer and provides an evidence-based approach to management. In addition, this review summarizes data on the health-related quality of life associated with current antineoplastic strategies, as well as critical issues facing patients and families along the disease trajectory.To provide optimal, appropriate care for patients with advanced-stage pancreatic cancer, ongoing assessment of their quality of life and of their preferences for treatment towards the end of life is crucial.