Combinatorial chemistry has become a major focus of research activity in the pharmaceutical industry for development new therapeutic compounds. The same techniques could be potentially applied to benefit agricultural and food research. This article reviews the various procedures used in combinatorial chemistry, outlines some of the strengths and limitations of the various methods, and proposes potential areas in agriculture and food that could be benefited by this technology. These areas include developing new antimicrobial agents, antioxidants, and other additives, creating antigen-binding molecules for the detection or removal of food pathogens or toxicants, engineering food proteins and enzymes for specific functions, and modifying biosynthetic pathways for the production of novel natural products.