Nisin is a ribosomally synthesized peptide that has broad-spectrum antibacterial activity, including activity against many bacteria that are food-spoilage pathogens. Nisin is produced as a fermentation product of a food-grade bacterium, and the safety and efficacy of nisin as a food preservative have resulted in its widespread use throughout the world, including the U.S. Nisin is a member of the class of antimicrobial substances known as lantibiotics, so called because they contain the unusual amino acid lanthionine. Lantibiotics, in general, have considerable promise as food preservatives, although only nisin has been sufficiently well characterized to be used for this purpose. As the number of known natural lantibiotics has increased and their useful characteristics have been explored, it has become desirable to synthesize structural analogs of nisin and other lantibiotics that do not occur naturally. The fact that lantibiotics are gene-encoded peptides synthesized by transcription and translation allows structural variants to be generated by mutagenesis. This review focuses on the progress that has been made in the construction and biological expression of genetically engineered nisin structural analogs. For example, a host-vector pair has been engineered that permits the construction of mutants of the structural gene for subtilin, which is a naturally occurring structural analog of nisin. The vector is designed in such a way that the mutant gene can be substituted for the natural subtilin gene in the chromosome of Bacillus subtilis, which in turn directs the transcription, translation, posttranslational modifications, and secretion of the mature form of the structural analog. Several structural analogs have been constructed, and their properties have provided insight into some of the structure-function relationships in lantibiotics, as well as their mechanism of antimicrobial action. These advances are assessed together with potential problems in the future development of nisin analogs as valuable new food preservatives.