The oncogene AKT (also called protein kinase B (PKB)) signals to the translational machinery, and activation of protein synthesis by Akt is associated with cancer formation. Akt directly stimulates the activity of translation initiation factors and upregulates ribosome biogenesis. Activation of protein synthesis by Akt is phylogenetically conserved from Drosophila to humans, and is important for regulating cell growth, proliferation and cell survival. Consequently, translation defects due to aberrant Akt activation may be a crucial mechanism leading to tumorigenesis. However, few in vivo studies have established a causative role for aberrant protein synthesis control in cancer. A major challenge in the future will be to identify the specific mRNAs regulated at the level of translation control directly relevant for cellular transformation. In this review, we highlight and discuss the emerging molecular and genetic evidence that support a model by which deregulation of specific or global protein synthesis contributes to cancer.