Currently, pancreatic cancer is fatal in over 90% of cases. Complete resection (if possible) is required for cure but the optimal adjuvant therapy is controversial. Given that pancreatic cancer frequently recurs both locoregionally and distantly, oncologic principles support the role of both adjuvant chemotherapy and radiotherapy. The historic trials evaluating chemoradiotherapy are too limited to provide clear guidance, but when viewed together with single institution data they suggest that chemoradiotherapy is beneficial. New data strongly support the use of adjuvant gemcitabine chemotherapy, but the benefit of the addition of radiation is still under investigation and no consensus exists on a standard of care. Clearly, no combination of currently available agents is sufficient to provide acceptable cure rates in pancreatic cancer and novel therapies must be found.