This talk will evaluate whole-genome sequencing as a new tool to identify persistent Listeria monocytogenes in food-associated environments. The critical assumptions are two. First—that to eliminate contamination by a persistent strain, we first need to identify that the contamination is, in fact, due to a persistent strain rather than sporadic re-contamination (to apply appropriate interventions). Second—that isolates of a persistent strain will be more closely related than isolates from a sporadic contamination event. Under this paradigm, whole-genome sequencing is emerging as the gold-standard subtyping tool for Listeria, and for good reason: analyses of these data provide nearly perfect resolution of differences at the single nucleotide level. This presents a new reality for pathogen subtyping because we can no longer apply the rule of thumb that isolates which appear indistinguishable represent distinct strains. Instead, we can use phylogenetics and other genomic analyses to identify when closely related isolates are likely to represent persistent strains. These analyses can shed light on several questions: How many SNP count as a close genetic relationship? What are the implications of mobile elements on subtyping? And how might government, academic, and industry even conduct these sophisticated analyses? This talk will address these questions through a survey of recent developments and results from a case study in a related food environment, using whole-genome sequencing of hundreds of Listeria from 30 retail delis to identify persist strains.