Epidemiological research has established a link between the widely used insulin-lowering drug metformin and a decrease in cancer incidence. Previous studies have shown that metformin inhibits growth of cancer cell lines, and, now, a new study by Kevin Struhl and colleagues suggests that metformin inhibits the inflammatory response required for cancer cell transformation (Proc. Natl. Acad. Sci. USA, published online 31 December 2012; doi:10.1073/pnas.1221055110). In this study, the authors used an inducible model of cellular transformation in which signs of an inflammatory response are rapidly evident after induction, with NF-κB activation seen within 15 min. Treatment with metformin inhibited the NF-κB response, but only when added soon after induction, suggesting that metformin works at an early stage. Previous work had suggested that metformin selectively kills a cancer stem cell (CSC)-like population in mice, and the authors show that metformin selectively inhibits NF-κB and STAT3 activities in these CSC-like cells. Previous work also had suggested that, in combination with standard chemotherapeutic agents, metformin prolongs remission in mouse tumors. In the current study, the authors show that metformin blocks the inflammatory pathway in such tumors, and this inhibition was correlated with prolonged remission in mice. Future work should focus on defining the mechanisms by which metformin blocks the inflammatory response in cancer.