Oncogenic activation of KRAS rewires the urea cycle to facilitate DNA synthesis in non-small cell lung cancer. This KRAS-driven metabolic reprogramming results in a deficiency in arginine biosynthesis and creates a dependency on the arginine transporter SLC7A1 to import extracellular arginine for tumorigenic growth. SLC7A1 is a targetable vulnerability in KRAS-mutant non-small cell lung cancer (represented on the cover as an Achilles’ heel), highlighting the potential utility of SLC7A1 inhibition as a therapeutic approach for treating these tumors. For details, see article by Gai and colleagues on page 1963.