The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic cancer was initially shown to be beneficial on the basis of a prospective, randomized trial published in 1985. Since then, oncologists have debated whether chemotherapy, chemoradiation, or both is optimal adjuvant therapy after pancreatectomy for ductal adenocarcinoma of the pancreas; no global consensus has emerged. Unfortunately, despite the completion of a number of subsequent randomized trials of adjuvant therapy since 1985, no further improvements in overall survival have materialized. This lack of progress is not simply the result of ineffective systemic therapies, but in part the result of poor trial design and calls for a more disciplined approach to the selection of patients for surgery, pathologic assessment of surgical resection margins, and postoperative (pretreatment) imaging. This is the only way to ensure that patients who receive adjuvant therapy are actually receiving therapy for radiographically occult possible microscopic disease, rather than therapy for incompletely resected locally advanced disease or early postoperative metastases. A critical analysis of completed adjuvant trials will be provided and a framework for the conduct of future trials of adjuvant therapy proposed.