Pancreatic ductal adenocarcinoma (PDA) remains a highly lethal disease; new therapeutic modalities are urgently needed. A number of immunotherapies tested in preclinical models have shown promise. Early-phase clinical trials have demonstrated evidence of immune activation that in some cases correlates with clinical response. Moreover, recent evidence delineates the intricate role of inflammation in PDA, even at its earliest stages. Pancreatic ductal adenocarcinoma is thus ripe for immunotherapy; however, significant challenges remain before success can be realized. Future studies will need to focus on the discovery of novel PDA antigens and the identification of the multiple immune suppressive pathways within the PDA tumor microenvironment that inhibit an effective PDA-targeted immune response. Technologies are now available to rapidly advance discovery. Rapid translation of new discoveries into scientifically driven clinical trials testing combinations of immune agents will likely continue to shift the procarcinogenic tumor environment toward the most potent anticancer response.