The seven mammalian sirtuins have been implicated in processes as diverse as gene expression, cell survival, angiogenesis, motility and the regulation of energy metabolism. Given this overabundance of sirtuin functions, there is great interest in their potential to address a broad range of diseases, including cancer. It has been described that the expression of different sirtuins is deregulated in many cancers. Depending of the cellular context, sirtuins can act as tumor suppressors and their down-regulation could facilitate tumorigenesis and, conversely, different sirtuins are overexpressed in some cancers facilitating several hallmarks of tumorigenesis, such as cell proliferation, apoptosis inhibition, angiogenesis induction, metabolic reprogramming, the promotion of epithelial mesenchymal transition, and migration. In the context where sirtuin activity is overrepresented, the use of sirtuin inhibitors is rising as a novel strategy to fight against cancer. In this chapter we review the potential use of sirtuins inhibitors in cancer treatment.