Pancreatic ductal adenocarcinoma (ie, pancreatic cancer) is among the most devastating of human malignancies. It is commonly diagnosed at advanced, already metastatic, and, hence, incurable stages. Despite extensive research efforts in recent decades, pancreatic cancer remains resistant to almost all clinically available therapy regimens. Recent advances in our understanding of the underlying pathophysiology and molecular biology have opened up avenues for the development of novel diagnostic and therapeutic strategies, some of which have shown highly promising preclinical results and are currently being translated into clinical application. Here in we present a review of recent literature on the molecular genetics of pancreatic cancer and emphasize clinical implications for the development of novel diagnostic and therapeutic approaches.