Pancreatic cancer is still a malignant disease of grim prognosis despite all therapeutic efforts. Because clinical symptoms in the early stage are usually absent or aspecific, it is frequently discovered at advanced or metastatic stage, only around 15-20% of tumors are resectable. In the majority of patients only the chemotherapy offers a prolongation of life, but even the first-line chemotherapeutic agent, the gemcitabine has a modest survival benefit, and objective tumor response is rarely achieved. Combination of various cytostatics did not produce a significant improvement either. For that reason, continuous search for other agents is mandatory. Nowadays, in the era of molecular-targeted oncotherapeutic approaches, pancreatic cancer is also a subject such trials: epidermal growth factor receptor blockade, inhibition of angiogenesis, modulation of tumor response through the extracellular matrix, inhibition of cyclooxygenase-2, farnesyl transferase inhibitors, signal transduction inhibitors, ablation of the hormonal influence and some other aspects have all been studies, but to date, no breakthrough in the treatment of pancreatic carcinoma is proven. In several Phase II-III studies these compounds given alone displayed marginal effects, but when combined with the standard cytostatics, some beneficial effects were observed, however, some of them displayed a severe (sometimes fatal) toxicity. To date, the role of the molecular targeted therapy in pancreatic carcinoma is promising, but the results are not convincingly superior to the standard chemotherapeutic treatments. Pancreatic adenocarcinoma remains a great challenge for the oncologists, and continuous search for better molecules and/or combinations is inevitable.