Cholera remains a significant global health burden. The causative agent responsible for the ongoing cholera pandemic, which began in 1961, is the seventh pandemic El Tor (7PET) lineage of . Over the past century, lineages of have been traced using phage typing schemes, DNA hybridization on microarrays and, more recently, comparative genomics enabled by next-generation sequencing. Such lineage tracing has provided essential insights into cholera transmission dynamics. Beyond their use as tools in typing schemes, phages have long been recognized as major players in cholera epidemiology. Importantly, the integration of comparative genomics, epidemiology and molecular studies has recently provided compelling evidence that bacterial defence systems, along with the evolutionary adaptations of phages to counteract them, play critical roles in the ongoing arms race between pandemic and their phages, with phage resistance likely influencing cholera epidemiology. In this review, we explore abundant and sporadic defence systems in sub-lineages of 7PET and describe how they protect their bacterial hosts from predatory phages. Additionally, we contrast these findings with the defence activities observed in the sixth pandemic classical lineage of . Finally, we discuss the experimental challenges and limitations associated with studying defence systems in and propose future directions to advance research in this field.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.