Abstract Within natural ecosystems, most plants are resistant to most pathogens. At a fundamental level, this seemingly simply truth may hold the key to our understanding of how plants have evolved to survive under a myriad of environmental conditions and their associated stresses. Indeed, in defining how plants evolve, adapt and maintain broad spectrum resistance to most pathogens – typically referred to as non‐host resistance – we may not only reveal the mechanisms that underpin plant resistance signalling but also the precise manner in which plants regulate these processes under various environmental conditions. Herein lies the greatest challenge and unanswered question in the field of agriculture today: How do we feed 9 billion people by the year 2050? To address this, one of the first hurdles that must be overcome is a full understanding of the processes that regulate stress (i.e. abiotic and biotic) signalling in plants, as well as the processes that define pathogen and host specificity, including the performance of these processes under rapidly changing environmental conditions. In the case of pathogen infection, plants utilise a broad suite of innate and inducible mechanisms to resist invasion. In large part, these processes are governed by the activity of resistance (R) proteins, which are evolutionarily conserved and highly evolved proteins that function not only in pathogen recognition but also in the activation of the cellular processes necessary to defend against proliferation and the elicitation of disease. Furthermore, recent data supports the hypothesis that numerous processes, such as the balance between growth and defence, also contribute to the host resistance and pathogen virulence. Key Concepts Most plants are resistant to most pathogens. Modern agriculture practices positively impact crop yield and durability. These practices can also have a negative impact on the unintended selection and enrichment of virulent pathogens. Plants defend against pathogen invasion using a suite of highly conserved resistance ( R ) genes. Pathogens have evolved to recognise and respond to the activity of plant R proteins through the deployment of secreted virulence factors. Immune signalling in plants utilises various pre‐formed and inducible processes to defend against pathogen infection. Many basic physiological processes, including response to light, temperature and water availability, are associated with, and required for, immune signalling. The development of advanced genome sequencing technologies has increased the speed at which the development and selection of elite breeding lines are deployed into cropping systems. Current plant breeding approaches utilise a hybrid of molecular genomics and classical breeding techniques to identify and introduce desirable traits into crops to enhance plant performance (e.g. resistance) and yield.