Genetically controlled resistance provides plant breeders with an efficient means of controlling plant disease, but this approach has been constrained by practical difficulties associated with combining many resistance genes together and strong evolutionary responses from pathogen populations leading to subsequent resistance breakdown. However, continuing advances in molecular marker technologies are revolutionizing the ability to rapidly and reliably manipulate resistances of all types – major gene, adult plant and quantitative resistance loci singly or multiply into individual host lines. Here, we argue that these advances provide major opportunities to deliberately design deployment strategies in cereals that can take advantage of the evolutionary pressures faced by target pathogens. Different combinations of genes deployed either within single host individuals or between different individuals within or among crops, can be used to reduce the size of pathogen populations and generate patterns of disruptive selection. This will simultaneously limit immediate epidemic development and reduce the probability of subsequent evolutionary change in the pathogen for broader infectivity or increased aggressiveness. The same general principles are relevant to the control of noncereal diseases, but the most efficacious controls will vary reflecting the range of genetic options available and their fit with specific ecology and life-history combinations.