To identify genes and pathways that cells can use to survive when glucose — an important source of energy and carbon — is limited, Vamsi Mootha, and colleagues performed genome-wide genetic screens and a PRISM growth assay. They found that cells ranging from healthy immune cells to cancer cells can use uridine, a component of RNA, as an energy source when glucose is unavailable. Targeting the biochemical pathway that cells use to break down uridine-derived sugar could help treat cancers and metabolic disorders and tune the immune response.