Owing to its aggressiveness, late detection and marginal therapeutic accessibility, pancreatic ductal adenocarcinoma (PDAC) remains a most challenging malignant disease. Despite scientific progress in the understanding of the mechanisms that underly PDAC initiation and progression, the successful translation of experimental findings into effective new therapeutic strategies remains a largely unmet need. The oncogene MYC is activated in many PDAC cases and is a master regulator of vital cellular processes. Excellent recent studies have shed new light on the tremendous functions of MYC in cancer and identified inhibition of MYC as a likewise beneficial and demanding effort. This review will focus on mechanisms that contribute to deregulation of MYC expression in pancreatic carcinogenesis and progression and will summarize novel biological findings from recent in vivo models. Finally, we provide a perspective, how regulation of MYC in PDAC may contribute to the development of new therapeutic approaches.