The development and application of modern sequencing technologies have led to many new improvements in food safety and public health. With unprecedented resolution and big data, high-throughput sequencing (HTS) has enabled food safety specialists to sequence marker genes, whole genomes, and transcriptomes of microorganisms almost in real-time. These data reveal not only the identity of a pathogen or an organism of interest in the food supply but its virulence potential and functional characteristics. HTS of amplicons, allow better characterization of the microbial communities associated with food and the environment. New and powerful bioinformatics tools, algorithms, and machine learning allow for development of new models to predict and tackle important events such as foodborne disease outbreaks. Despite its potential, the integration of HTS into current food safety systems is far from complete. Government agencies have embraced this new technology, and use it for disease diagnostics, food safety inspections, and outbreak investigations. However, adoption and application of HTS by the food industry have been comparatively slow, sporadic, and fragmented. Incorporation of HTS by food manufacturers in their food safety programs could reinforce the design and verification of effectiveness of control measures by providing greater insight into the characteristics, origin, relatedness, and evolution of microorganisms in our foods and environment. Here, we discuss this new technology, its power, and potential. A brief history of implementation by public health agencies is presented, as are the benefits and challenges for the food industry, and its future in the context of food safety.