Plant pathogens can emerge in agricultural ecosystems through several mechanisms, including host-tracking, host jumps, hybridization and horizontal gene transfer. High-throughput DNA sequencing coupled with new analytical approaches make it possible to differentiate among these mechanisms and to infer the time and place where pathogens first emerged. We present several examples to illustrate the different mechanisms and timescales associated with the origins of important plant pathogens. In some cases pathogens were domesticated along with their hosts during the invention of agriculture approximately 10,000 years ago. In other cases pathogens appear to have emerged very recently and almost instantaneously following horizontal gene transfer or hybridization. The predominant unifying feature in these examples is the environmental and genetic uniformity of the agricultural ecosystem in which the pathogens emerged. We conclude that agro-ecosystems will continue to select for new pathogens unless they are re-engineered to make them less conducive to pathogen emergence.