The desire globally by consumers to have fresh microbiological safe and ready-to-eat foods requires the development of novel natural antimicrobials. The complex range of microbes associated with food and diverse intrinsic properties of food limit the application and efficacy of many antimicrobials. Essential oils derived from plants show promise, but their application is limited since they can impart off-odors and flavors. Use of bacteriocins is generally limited to the control of Gram-positive microbes. In some instances, methods that are effective, such as bacteriophages, have a negative consumer perception. The potential exists to use natural antimicrobials with existing and novel technologies such as high pressure or thermal processing as part of a hurdle approach to improve the microbial safety and quality of food. This chapter is focused on a few categories of natural antimicrobials that have garnered considerable attention in recent years.