Chemotherapy is proven to play a central role in the adjuvant management of pancreatic cancer. A number of studies have validated its small but significant survival benefit to patients following surgical resection, but many questions about the optimal adjuvant chemotherapeutic management of pancreatic cancer still persist. Currently, the benefits of both the chemotherapeutic agents gemcitabine and 5-fluorouracil have been validated as adjuvant options, with a preference for gemcitabine emerging based on its greater tolerability. Methods to individualize the selection of an adjuvant agent based on an individual tumor's characteristics are being explored, and additional novel agents and regimens are actively being investigated. In the studies that established chemotherapy's adjuvant benefit, a controversy simultaneously developed as to the role of the concurrent use of adjuvant radiation therapy in addition to chemotherapy, leading to the development of a conflicting consensus on how to adjuvantly manage pancreatic cancer patients. Chemotherapy given concurrently with radiation therapy has emerged as the preferred adjuvant approach in the United States, whereas chemotherapy alone is preferred in Europe. In addition to the debate over modality, a separate debate of treatment timing has emerged from studies of neoadjuvant therapy, which has demonstrated a survival benefit in the management of pancreatic cancer, but has not been directly compared with postsurgical adjuvant therapy. This review discusses the evidence for chemotherapy in the adjuvant management of pancreatic cancer, including both the choice of agent and value of concurrent radiation therapy, as well as future directions with novel agents and regimens, techniques of response prediction, and timing to postsurgical adjuvant versus neoadjuvant therapy.