Sirtuins are involved in the control of the cell cycle and regulation of gene transcription. While some sirtuins have tumor suppressor effects, others regulate tumors metabolism. Within this perspective, the present article is a review of the current role of sirtuins in the etiology and physiopathology of cancer. Sirtuins show strong potential to become a valuable predictive and prognostic marker for cancer and are eligible as therapeutic targets for a variety of tumors. Investigation of new molecules able to modulate sirtuins activity must be encouraged.