Immunotherapeutic approaches have created effective therapy with a manageable toxicity profile as a new treatment approach in a wide variety of cancers, often leading to longer responses and control of disease. In pancreatic cancer, responses to immunotherapy have been difficult to capture. Many obstacles have been identified in the limited efficacy of immunotherapy in pancreatic cancers. The hostile tumor microenvironment plays a large role in therapeutic development of immune-based therapies in pancreatic cancer. The approach to addressing many of these challenges will require a team-based approach to optimize both our understanding of the disease, its microenvironment, and how each component behaves in the development and growth of pancreatic cancer as well as the mechanisms used to best create therapies and combinations of treatment that will have long-standing efficacy for pancreatic cancer patients.