During intracellular replication, the bacterial pathogen Chlamydia trachomatis modulates stress-related signalling pathways to maintain host cell viability and thereby ensures completion of its life cycle. González et al. show that C. trachomatis induces the degradation of p53, a key host factor involved in apoptosis, to prevent host cell death. p53 degradation was mediated by MDM2, a ubiquitin ligase that ubiquitylates p53 and targets it for proteasomal degradation. Furthermore, inhibition of the p53–MDM2 interaction prevented p53 degradation in infected cells and led to a decrease in infectious progeny, which suggests that the pathogen was unable to complete its normal developmental cycle. Finally, blocking MDM2-induced p53 degradation re-sensitized infected host cells to apoptotic stimuli. In sum, this study reveals a mechanism whereby C. trachomatis interferes with the stress response of the host to ensure its own survival.