<p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Although surgical resection is the only potentially curative option, recurrence from microscopic residual disease develops in more than half of these patients, underscoring the importance of adjuvant chemotherapy. Over the past two decades, multiple randomized controlled trials have demonstrated that adjuvant chemotherapy can improve the disease-free and overall survival of patients with resected PDAC significantly. Although S-1 monotherapy became the standard of care in Japan following the JASPAC-01 trial, gemcitabine-based regimens are still used widely in Western countries. This review provides an overview of key clinical trials supporting adjuvant chemotherapy, including an introduction of the 2022 Clinical Practice Guidelines for Pancreatic Cancer in Japan and the current NCCN Guidelines for Pancreatic Adenocarcinoma. We also discuss some of the problems that remain unresolved, such as for how long and when adjuvant therapy should be given. Moreover, there is still insufficient evidence for certain subgroups of patients, such as those with borderline resectable or initially unresectable PDAC. Thus, new treatments, such as immune checkpoint inhibitors, may be useful in future. More clinical studies are needed to establish the most appropriate regimens, as adjuvant chemotherapy should be selected based on patient age, tumor stage, and prior treatment.</p>