Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies in the United States. Improvements in imaging have permitted the categorization of patients according to radiologic involvement of surrounding vasculature, i.e., upfront resectable, borderline resectable, and locally advanced disease, and this, in turn, has influenced the sequence of chemotherapy, surgery, and radiation therapy. Though surgical resection remains the only curative treatment option, recent studies have shown improved overall survival with neoadjuvant chemotherapy, especially among patients with borderline resectable/locally advanced disease. The role of radiologic imaging after neoadjuvant therapy and the potential benefit of adjuvant therapy for borderline resectable and locally advanced disease remain areas of ongoing investigation. The advances made in the treatment of patients with borderline resectable/locally advanced disease are promising, yet disparities in access to cancer care persist. This review highlights the significant advances that have been made in the treatment of borderline resectable and locally advanced PDAC, while also calling attention to the remaining challenges.