Plant resistance (R) genes are highly effective to protect plants against diseases, but pathogens can overcome such genes relatively easily by adaptation. Consequently, in many cases R genes do not confer durable resistance in agricultural environments. One possible strategy to make the use of R genes more sustainable depends on the significantly improved in all lines in the greenhouse and the field, both with naturally of R genes, we overexpressed in wheat the Pm3b resistance gene against powdery mildew under control of the maize ubiquitin promoter. Four independent transgenic lines were tested in the greenhouse and the field during three years. The four lines showed a five- to 600-fold transgene overexpression compared to the expression of the endogenous Pm3b gene in the landrace “Chul”. Powdery mildew resistance was morphology. The highest overexpressing line had the strongest side effects, suggesting occurring infection or after artificial inoculation. Under controlled environmental conditions, the line with the strongest overexpression of the Pm3b gene showed a dramatic increase in resistance to several independent isolates that are virulent on the endogenous Pm3b. Under a variety of field conditions, but never in the greenhouse, three of the four transgenic lines showed pleiotropic effects on spike and leaf a correlation between expression level and phenotypic changes. These results demonstrate that the successful transgenic use of R genes critically depends on achieving an optimal level of their expression, possibly in a tissue specific way.