Pancreatic cancer remains a formidable challenge for oncologists. The only curative option remains surgical resection in early-staged disease. Cytotoxic chemotherapy offers a modest survival benefit in the advanced or metastatic stage. Clinical trials of therapy have not yet yielded encouraging outcomes in advanced pancreatic cancer. In this review, we highlight recent developments in therapy focusing on trials conducted in the advanced or metastatic setting and offer insight into the challenges for future studies.