Plant diseases represent a major constraint on agricultural production. Finding sustainable novel means for their control is an important challenge. The ever-increasing knowledge and understanding of plant-microbe interactions has led to several ingenious transgenic approaches to combat disease. The first transgenic disease-resistant plants expressed single or a few stacked genes encoding antimicrobial proteins. Whereas the first attempts were disappointing in the field, several examples from recent field studies are promising and some of these use ingenious designer approaches. Less progress has been made with antimicrobial metabolites where the challenges lie in obtaining biosynthetic genes and in coordinating their expression. The increased understanding of the processes regulating plant defence (plant immunity) and modes of action of pathogen effector proteins have also led to novel strategies for designing resistant plants. The most promising of these is host-induced gene silencing that targets specific pathogens, either the effectors or, preferably, essential housekeeping genes. With these approaches, and several maverick examples of "genes pulled out of a hat," the technical effort in designing resistant plants is finally paying off. The prospects are good, biologically speaking, but can industry deliver? There is still an issue of public acceptance of genetic engineering of crop plants, especially in Europe; so whilst considerable strategic and practical progress has been made over the last decade, vanishingly few products have been adopted by agriculture. Some of these have been in use for over two decades. As yet, all are against viral diseases and not against diseases caused by microorganisms.