Recent applications of techniques in plant molecular biology and biotechnology to the study of host?pathogen interactions have resulted in the identification and cloning of numerous genes involved in the defense responses of plants following pathogen infection. These include: genes that express proteins, peptides, or antimicrobial compounds that are directly toxic to pathogens or that reduce their growth in situ; gene products that directly inhibit pathogen virulence products or enhance plant structural defense genes, that directly or indirectly activate general plant defense responses; and resistance genes involved in the hypersensitive response and in the interactions with avirulence factors. The introduction and expression of these genes, as well as of antimicrobial genes from nonplant sources, in a range of transgenic plant species have shown that the development of fungal pathogens can be significantly reduced. The extent of disease reduction varies with the strategy employed as well as with the characteristics of the fungal pathogen, and disease control has never been complete. Manipulation of salicylic acid, ethylene, and cytokinin levels in transgenic plants have provided some interesting results with regard to enhanced disease tolerance or susceptibility. The complex interactions among the expressed gene product, plant species, and fungal pathogen indicate that the response of transgenic plants cannot be readily predicted. Combinations of defense gene products have shown considerably more promise in reducing disease than single-transgene introductions. The use of tissue-specific or pathogen-inducible promoters, and the engineered expression of resistance genes, synthetic antimicrobial peptides, and elicitor molecules that induce defense responses have the potential to provide commercially useful broad-spectrum disease resistance in the not-too-distant future. The issues and challenges that will need to be addressed prior to the widespread utilization of these transgenic plants are highlighted.