Cancer cells require the biosynthesis of structural components for biomass production. This requires a reprogramming of the metabolic pathways to ensure that nutrients such as glucose and glutamine are not completely oxidized but instead their intermediary metabolites are shunted into biosynthetic pathways. Activation of the mammalian Target of Rapamycin Complex 1 (mTORC1) has been correlated with increased nutrient uptake and metabolism, but no molecular connection to glutamine metabolism has been reported. A recent paper from the Blenis Lab (Csibi et al., Cell, 2013) showed that mTORC1 activation regulates glutamine anaplerosis by promoting the conversion of glutamine to α-ketoglutarate, a tricarboxylic acid (TCA) cycle intermediate. Csibi and colleagues found that mTORC1 promotes the activity of glutamate dehydrogenase (GDH). The authors sought to identify how this occurred and found that SIRT4, an inhibitor of GDH, was repressed by mTORC1. The molecular detail of this repression involved the mTORC1-mediated phosphorylation and proteasome-mediated degradation of CREB2, a transcription factor that binds the SIRT4 human promoter. The expression of SIRT4 mRNA was decreased in several human cancers, and its forced expression in cancer cells significantly repressed proliferation, and resulted in reduced tumor development in a TSC-xenograft model. These findings suggested that targeting glutamine metabolism might impair the growth or survival of cancer cells. Indeed, the authors found that the combined pharmacological inhibition of glucose and glutamine metabolism selectively sensitized mTORC1-active cells to undergo cell death. Altogether, these results point to a central role for mTORC1 in the regulation of glutamine metabolism and suggest that the use of glutamine metabolism inhibitors may prove efficacious in nutrient-dependent cancers with high mTORC1 signaling.