The evolutionary arms race between prokaryotes and their viruses has resulted in the development of sophisticated anti-phage defence mechanisms, including restriction–modification and CRISPR–Cas systems. Now, Maxwell and colleagues report a new chemical anti-phage defence system that is widespread in Streptomyces spp. They show that Streptomyces spp. produce secondary metabolites (daunorubicin and doxorubicin) that intercalate into phage DNA and block phage replication, whereas other DNA-intercalating agents did not elicit this effect. Furthermore, these molecules did not affect bacterial growth. Daunorubicin was found to act very early in the phage life cycle, after DNA ejection but before DNA replication. This suggests that these molecules act at a stage that is unique to phage DNA replication, such as genome circularization. The authors also provide data that are consistent with a model in which metabolites can diffuse into bacteria and protect them from infection.