Host–pathogen interactions in natural plant communities were generally overlooked until the 1970s when plant pathologists and evolutionary biologists started to take an interest in these interactions. This article introduces the general principles of plant pathosystems, provides a basic critical overview of current knowledge of host–pathogen interactions in natural plant pathosystems, and shows how this knowledge is important for future developments in plant pathology. Plant pathosystems can be further divided according to the structure and origin of control, as autonomous (wild plant pathosystems, WPPs) or deterministic (crop plant pathosystems, CPPs). WPPs are characterised by the disease triangle and closed-loop (feedback) controls, CPPs are characterized by the disease tetrahedron and open-loop (nonfeedback) controls. Basic general, ecological, genetic and population structural and functional differences between WPPs and CPPs are described. It is evident that we lack a focus on long-term observations and research of diseases and their dynamics in natural plant populations, metapopulations, communities, ecosystems and biomes, as well as their direct or indirect relationships to crop plant pathosystems. Differences and connections between WPPs and CPPs, and why these are important for agriculture are demonstrated through a case study of lettuce (Lactuca spp.) and lettuce downy mildew (Bremia lactucae). Research on interactions between pathosystems, the “cross-talk“ of WPPs and CPPs, is still very limited and, as shown in interactions between wild and cultivated Lactuca spp. – B. lactucae associations, can be highly complex. The implications and applications of this knowledge in plant breeding, crop management and disease control measures is considered.