Metabolic reprogramming in cancer cells is linked to upregulated glutaminolysis, which contributes to pancreatic cancer survival. Oncogenic KRAS-induced NRF2 mediates chemoresistance, whereas it also causes metabolic rewiring and elevates pathways involved in glutamine metabolism. Blocking glutamine metabolism prevents cancer cells from resisting chemotherapy, which indicates that targeting glutaminolysis is a potential therapeutic strategy for pancreatic cancer patients. In combination with gemcitabine, this treatment appears to be a promising therapeutic strategy. Cover artwork by Ella Marushchenko. For details, see article by Mukhopadhyay and colleagues on page 1630.