Pancreatic cancer is considered an aggressive malignancy that responds poorly to current treatments and therefore has a dismal survival rate. This disease is usually not diagnosed until a late stage, at which point palliative chemotherapy with the purine analogue gemcitabine and/or a fluoropyrimidine or a platinum agent is the standard approach. There are some new data on the molecular and genetic changes that take place in pancreatic cancer, which may facilitate the accuracy of diagnosis and efficacy of treatments. However, translational efforts in clinical practice have increased clinicians` options with a targeted agent, erlotinib, in combination with the standard gemcitabine chemotherapy. Many other novel drugs currently being tested in the field of pharmaco-oncology target various altered biological pathways and molecules. Nevertheless, the lack of clinically significant improvements in treatments is rendering efforts to develop methods of early diagnosis both more urgent and promising. The aim of this review was to summarize the molecular basis of pancreatic carcinogenesis and the latest developments in diagnosis by molecular means, focusing on the results of clinical research into targeted and personalized treatments. (Gut Liver 2010;4:433-449)