Naturally occurring antimicrobial compounds could be applied as food preservatives to protect food quality and extend the shelf life of foods and beverages. These compounds are naturally produced and isolated from various sources, including plants, animals and microorganisms, in which they constitute part of host defense systems. Many naturally occurring compounds, such as nisin, plant essential oils, and natamycin, have been widely studied and are reported to be effective in their potential role as antimicrobial agents against spoilage and pathogenic microorganisms. Although some of these natural antimicrobials are commercially available and applied in food processing, their efficacy, consumer acceptance and regulation are not well defined. This manuscript reviews natural antimicrobial compounds with reference to their applications in food when applied individually or in combination with other hurdles. It also reviews the mechanism of action of selected natural antimicrobials, factors affecting their antimicrobial activities, and future prospects for use of natural antimicrobials in the food industry.