Pancreatic cancer is the fourth leading cause of cancer death, associated to both limited success in treatment and a poor prognosis. The wide number of signalling pathway aberrations contributing to the tumorigenesis, progression and drug resistance, is the main reason for treatments being unsuccessful to date in pancreatic cancer. An additional and still under-investigated intracellular cancer target is the peroxisome proliferator activated receptor gamma (PPAR-γ). Notwithstanding, several studies have shown the in vitro antitumor activity of PPAR-γ agonists in cancer cells, such agents, if used in monotherapy, were poorly effective in cancer treatment. The present review will focus on the potential therapeutic role of PPAR-γ agonists in combination with other drugs (type I interferons, gemcitabine and COX-2 inhibitors), highlighting molecular interactions and signalling pathways involved in pancreatic cancer cells. Understanding of the underlying molecular mechanisms and survival pathways activated in cancer cells should promote the development of new targeted and more successful therapies in the future.