Powdery mildew (PM) is one of the most common plant diseases in the world, occurring in many economically important food and ornamental crops. The characteristic symptoms of this disease are easily recognizable as a white powder that extends across the aerial parts of the plants. The causal pathogens of PM are obligate biotrophic fungi from the Erysiphales order that obtain nutrients from the living tissue of their hosts. To this day, chemical control of PM remains a common practice in many crops. However, the use of fungicides has a negative impact on the environment. For this reason, breeding for resistant varieties stands out as an essential tool to achieve a sustainable management of this disease.In tomato, PM is caused by Oidium neolycopersici (On), a polyphagous fungal species that threatens the production of this crop worldwide. The current understanding of this disease and the mechanisms through which plants are able to withstand it comes from the research done in two pathosystems. On the one hand, in the late 1980’s, an outbreak of On in cultivated tomato in Europe urged researchers to find natural sources of resistance to this disease. This drove the research on the identification of Resistance (R) loci in wild relatives of tomato. On the other hand, On can also infect the model plant Arabidopsis thaliana (Arabidopsis). This model organism offers many advantages for research due to the availability of a large number of scientific resources and information. Apart from On, Arabidopsis is a host for three more PM species. Hence, the Arabidopsis-PM pathosystems have been widely used to identify genetic components of resistance and susceptibility. These latter components are particularly interesting, as they seem to be conserved for several species of PMs and can potentially be extrapolated to other plant species. The plant genes whose absence results in the inability of the pathogen to complete their life cycles, are named Susceptibility (S) genes. The use of S genes is proposed as a suitable alternative to obtain more durable, broad-spectrum resistance and is particularly important in the absence of R genes in certain crops. The work of this thesis focuses on the exploration and identification of new genetic components of resistance and susceptibility to On in both the model plant Arabidopsis and the crop plant tomato.In the first half of this thesis, we make use of Arabidopsis to identify genetic components of the natural resistance against On. In Chapter 2, I report the finding of a dominantly-inherited resistance in accession Bla-6. Through a series of recombinant analyses, we fine mapped the locus responsible for the resistance and used CRISPR/Cas9 to knockout the candidate genes. We show that targeted mutagenesis of the ZED1-RELATED KINASE 13 (ZRK13) in Bla-6 results in a susceptible phenotype, thus identifying this gene as a novel component of resistance against On. Furthermore, in Chapter 3, we found two major QTLs explaining resistance to On in accession Litva. Through an independently-executed fine-mapping effort we identified ZRK13 to be also required for resistance in this accession. However, an additional locus in chromosome 3 is needed for full resistance in Litva. In these two chapters I discuss the identity of this gene and suggest further steps to investigate the molecular mechanisms of this previously uncharacterized resistance component.The second half of this thesis focuses on the tomato-On interaction to study susceptibility and resistance components. In Chapter 4, I report the generation, through CRISPR/Cas9-targeted mutagenesis, of tomato knockouts of the susceptibility gene PMR4. This gene was first found in a forward genetic screening in Arabidopsis and resistance through its impairment was later found to be conserved in the tomato-On pathosystem. I describe the characterization of five different mutation events in the target gene and report a reduced but not complete loss of susceptibility upon inoculation with On. With this study, we set the basis for the CRISPR/Cas9-based protocol for gene identification that was later used in the other chapters of this thesis.In Chapter 5 I describe the fine-mapping and characterization of the candidate genes for Ol-1, a dominant resistance found in S. habrochaites accession G1.1560. We show that targeted mutagenesis of Solyc06g060800, a gene encoding a 2-oxoglutarate and Fe(II)-dependent oxygenase superfamily protein, results in increased susceptibility to PM in near-isogenic Ol-1 background. In this chapter we further discuss the implications of this finding.In Chapter 6 I give an overview of the results presented in this thesis and discuss their implications in the plant immunity model. Altogether, the work presented in this thesis contributes to the understanding of the diversity of genetic components of resistance against On in both Arabidopsis and tomato, with the aim of aiding in the development of breeding strategies that result in a sustainable management of this disease.