Pathogen reproduction tends to be host-frequency dependent, so that disease may be more problematic when particular crop species or genotypes are very common. Nonetheless, production agriculture is dominated by extensive monocultures. This is due partly to artifacts of agricultural policy and decision-making, but partly also to the real challenges of understanding and manipulating the ecological genomics of a single crop genotype, not to mention multiple species and genotypes. So there are trade-offs in investing agricultural research in many versus only a few agricultural species. Agricultural diseases may emerge or re-emerge for a number of reasons, including new pathogen introductions, new adaptation of pathogens to previously effective resistance genes, new types of host homogeneity (such as the widespread deployment of Texas male sterile cytoplasm in maize), trading policies that increase the economic impact of uncommon infections, and changes in the abiotic environment. Technological abilities in ecological genomics that are needed to support management of emerging and long-term disease include the ability to manipulate disease resistance genes in crops, the ability to devise crop plant communities at multiple spatial scales that are optimal for a range of agronomic traits, the ability to manipulate microbial communities for disease suppressive characteristics, and the ability to minimize undesired impacts on ecosystems surrounding agricultural systems. The construction of crop variety mixtures is an example of a technology that draws heavily on ecological ideas and has also contributed greatly to our understanding of disease ecology through experiments examining the effects of patterns of host variability on disease through time and space. New forms of agricultural systems, such as perennial grains, may also offer environmental benefits such as reduced erosion and nutrient leaching, but will also challenge ecological genomics to provide effective methods of disease management since pathogens may more easily accumulate in long-term agricultural stands. While agricultural systems have typically grown less diverse over the past century, advances in ecological genomics are likely to make it feasible for systems to incorporate higher levels of diversity in the future as agricultural scientists are better able to influence and manage complex agricultural communities for reduced disease.