Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer, due to both its late stage at diagnosis and its resistance to chemotherapy. However, recent advances in our understanding of the biology of PDAC have revealed new opportunities for early detection and targeted therapy of PDAC. In this review, we discuss the pathogenesis of PDAC, including molecular alterations in tumor cells, cellular alterations in the tumor microenvironment, and population-level risk factors. We review the current status of surveillance and early detection of PDAC, including populations at high risk and screening approaches. We outline the diagnostic approach to PDAC and highlight key treatment considerations, including how therapeutic approaches change with disease stage and targetable subtypes of PDAC. Recent years have seen significant improvements in our approaches to detect and treat PDAC, but large-scale, coordinated efforts will be needed to maximize the clinical impact for patients and improve overall survival.