Pancreatic adenocarcinoma is the eighth leading cause of cancer deaths worldwide in men and ninth leading cause in women. Surgical resection offers the only chance of potential cure; however, only 9.4% of patients present at the localized, resectable stage, whereas the rest present at the locally advanced or metastatic, unresectable stages. Because of the guarded outcomes following systemic chemoradiation and the associated systemic toxicities, locoregional therapies have recently gained popularity. Various endoscopic techniques (endoscopic ultrasound [EUS]–guided ablative therapies, fine-needle instillation of antitumor agents, stereotactic body radiation therapy with EUS-guided fiducial marker placement, and EUS-guided brachytherapy) have been explored over the past several years. Endoscopic therapy plays a role in the treatment of unresectable pancreatic adenocarcinoma. Its minimal invasiveness and increased precision of delivering oncologic treatments under EUS guidance render it as a favorable option for patients who do not benefit from surgical resection. New endoscopic therapies are currently under investigation, and the emerging role of the endoscopist in the treatment of unresectable pancreatic cancer continues to grow.