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The use of organic acids in the feed industry has collected a general consensus over the years because of their scientifically and practically proven efficacy on both health status and growth performance of animals. The application of in-feed organic acids as a pre-harvest intervention strategy to reduce food-borne pathogens intestinal colonization in food-animals is still in an early phase of study, but results seem to be promising. In this chapter we will discuss the mechanism of action of organic acids as antimicrobials and their use for in-feed applications. In particular, the effect of organic acids on food-borne pathogen virulence genes and, more generally, on the intestinal microflora will be reviewed. As the efficacy of organic acids is linked to their actual concentration at intestinal level, two techniques are proposed to enhance their “strength”: the use of combined strategies, such as the coupling of organic acids with aromatic compounds, that would allow to reduce the dose of inclusion in the feed, and microencapsulation techniques, that eventually allow the targeted release of organic acids at intestinal level, where colonization occurs. While organic acids antimicrobial properties in vitro are well documented and consistent, in vivo experiments, though encouraging, still deserve a deeper investigation, in order to better understand organic acids role on the complexity of microflora, mucosa, and diet crosstalk.