Ductal pancreatic adenocarcinoma is a dismal disease, having the worst prognosis of all solid tumors. While genomics and transcriptomics have provided a wealth of data, no contribution has been made to clinical medicine in terms of diagnostic or prognostic markers. Hope lies in yet another novel technology, proteomics. Conceptually, proteomics bears the advantage of incorporating both posttranslational modifications as well as host factors. This is thought to be important in factors influencing survival such as chemoresistance. This tutorial review discusses the state of the art in pancreatic cancer proteomics in light of technical developments. At this moment, proteomics is still at the beginning in clinical application. First results, however, suggest some hope for the development of a new understanding of the molecular biology in pancreatic cancer yielding into very specific markers of disease or allowing a rational and individualized therapy.