NUPR1, or p8 or com1, was first identified from rat pancreas during acute pancreatitis and later as a gene whose expression was upregulated in metastatic breast cancer cells. NUPR1 is a molecule whose expression is upregulated in response to stress and is hence influenced by the host microenvironment. While NUPR1 has been implicated in several diseases, there is no singular biochemical pathway that can be attributed to its role in cancer. NUPR1 has been found to aid the establishment of metastasis and to play a key role in the progression of several malignancies including those of breast, thyroid, brain and pancreas. NUPR1 has been implicated in inducing chemoresistance in pancreatic and breast cancer cells, protecting them from apoptosis and making tumor cells genetically unstable. In prostate cancer, however, NUPR1 appears to have tumor suppressive activity. Understanding the mechanism of action of the multifaceted functions of NUPR1 may open up new dimensions towards creating novel therapies against cancer as well as other pathologies. This review draws on several published studies on NUPR1, mainly in cancer biology, and assesses NUPR1 from the perspective of its functional role in making cancer cells resistant to the action of conventional chemotherapeutic drugs. © 2009 Springer Science+Business Media, LLC.