Pancreatic ductal adenocarcinoma is a devastating disease that represents an important health problem. It spreads rapidly at a time when patients have relatively few symptoms and consequently is often only detected at an advanced stage when treatment options are limited. Rapid developments in technology and bioinformatics have recently led to a surge in proteomics-based cancer research. Comparative analysis of protein profiles from nonmalignant and malignant pancreas cells or tissue, or from different stages of pancreatic cancer, potentially offer unique insight into the biology of this tumor type. Furthermore, proteomic approaches may provide novel diagnostic or therapeutic markers for this disease. Although such analyses are still in their infancy, they show great potential in the ongoing battle against this dismal disease.