Although in centers where pancreatectomy is performed frequently, associated morbidity and mortality rates have improved, long-term outcomes in pancreatic adenocarcinoma patients remain poor when surgery is the sole therapeutic modality. The impact of adjuvant chemotherapy on survival in patients with localized pancreatic cancer remains incompletely defined. The European Study Group for Pancreatic Cancer (ESPAC)-1 trial has suggested that overall survival rates are superior when chemotherapy is added to surgery, even when regimens believed to be relatively ineffective in the treatment of advanced disease are used. The role of radiotherapy given with chemotherapy is also unresolved, but chemoradiation continues to receive consideration in the multimodality approach to localized pancreatic cancer. Enhanced collaboration and increased involvement by pancreatic surgeons have helped in the recruitment of pancreatic cancer patients for large-scale randomized clinical trials in Europe and the United States. Many newer chemotherapeutic agents with efficacy in gastrointestinal cancers have yet to be investigated in the adjuvant and neoadjuvant settings.