Pests and diseases impact on crop yield and quality, and also reduce resource-use efficiency. Improved crop protection strategies to prevent such damage and loss can increase production and make a substantial contribution to food security. DNA-based technologies are likely to greatly increase the speed, sensitivity and accuracy of pest and pathogen detection and diagnosis. Rapid sequencing of nucleic acids from infected plants will aid identification of novel disease agents. Biomarkers of disease or crop damage such as volatile chemicals or blends may also be used to detect pest outbreaks. Biosensors coupled to information networks will provide real-time monitoring and surveillance of crops or stored produce and hence early warning of emerging problems and new invasive species. Challenges remain in the dissemination of new technologies and information to resource poor farmers in developing countries, although the rapid extension of the internet, mobile phones and other communication networks will provide new opportunities. Defining the genetic and molecular basis of innate plant immunity has been a major advance in plant biology with the potential to identify new targets for intervention via novel chemistry or genetic modification (GM). Identification of regulatory genes, signal molecules, pathways and networks controlling induced plant defence should lead to the development of a new generation of defence modulators, delivered either as crop protection products, or via biological agents on seeds or in the root zone. There should also be opportunities to select more responsive crop genotypes, or to develop transgenic crops tailored to respond to specific chemical cues or molecular patterns diagnostic for particular biotic threats. Sequencing of the genomes of the major crop species and their wild relatives will expand enormously the known gene pool and diversity of genetic resources available for plant breeders to access. It should be possible to identify genomic regions and genes conferring more durable, quantitative resistance to pathogens. The breeding cycle will be accelerated by high-throughput phenotyping and more efficient selection of resistance traits using within-gene markers. GM approaches will facilitate pyramiding (combining) resistance genes with different specificities and modes of action, thereby reducing the risk of directional selection for virulence. Analysis of the genomes of plant pathogens and invertebrate pests is already providing new information on genes, gene families and processes involved in host colonization and pathogenicity. Comparative genomics of species with diverse host ranges, contrasting feeding habits and different pathogenic lifestyles will identify new targets for inhibiting pest attack and aid the development of novel antimicrobial drugs and pesticides. Understanding the natural ecology of pests and pathogens, such as the factors determining host location, resource exploitation and interactions with other organisms, will improve our ability to manipulate behaviour, or exploit natural enemies or other antagonists of pest species. Volatile signals, either from natural plant sources, or engineered in transgenic crops, will be more widely used to modify pest behaviour. It may also be possible to manipulate microbial communities regulating pathogen populations and activity, and thereby recruit and retain more effective biocontrol agents. Insights into the natural diversity and activity of soil and microbial populations in the zones surrounding roots and seeds will provide new information on mechanisms of suppression regulating pest species. Fully effective interventions are unlikely, due to the complexity and diversity of the soil system, but there should be progress towards integrated control regimes combining more resistant crop genotypes (either selected or GM) with targeted management of natural suppressive processes. Harnessing new technologies and knowledge to create more durable resistant crops and sustainable disease and pest management systems will require improved understanding of the factors driving pest and pathogen adaptation and evolution. There must also be an increased emphasis on translational research and delivery, and developing strategies appropriate for lower-input production systems, if the second ‘green revolution’ is to become a reality.