Despite recent advances in diagnosis and treatment of certain cancers such as breast, colon and prostate cancers, pancreatic cancer remains a deadly malignancy with a mortality rate almost equal to its incidence. The survival benefit after all possible medical interventions is still disappointing for the majority of patients with pancreatic cancer. Improving the quality of life and increasing survival remain as the key objectives of pharmacogenomics and clinical investigation in pancreatic cancer. There are several notable genetic loci (e.g., RRM1, CDA, DPYD, UGT1A1) known to predict the toxicity of drugs used in pancreatic cancer such as gemcitabine, capecitabine, platinum agents and irinotecan. Other genes are associated with efficacy of these drugs (e.g., HuR, DCK, TS, ERCC1), although prospective validation of their clinical utility is still required. This paper presents the latest research advances in pharmacogenomics of pancreatic cancer with a view to molecular guidance for clinical diagnosis and individualized patient care.