Pancreatic cancer (PC) has an extremely high mortality with a five-year survival of only 5%. The cancer cells are accompanied by the desmoplastic stroma produced by cancer-associated fibroblasts (CAFs). Pancreatic stellate cells are the most important source of CAFs. Several studies indicate that the desmoplastic stroma reduces the effect of radio- and chemotherapy, but experimental reduction of desmoplasia and CAFs leads to more aggressive cancers. Hence, the exact role of desmoplasia in PC remains to be elucidated, and future studies should also include human pancreatic tissue.