The unique plant resistance (R) protein RPW8.1 and RPW8.2 confers broad-spectrum resistance in Arabidopsis to all tested isolates of Golovinomyces spp. fungi, the casual agents of powdery mildew disease in multiple plant species. RPW8.2 is specifically targeted to the extra-haustorial membrane (EHM) that encases the fungal feeding structure named the haustorium and represents the host-pathogen interface. EHM-localization of RPW8.2 correlates with haustorium-targeted host defense, providing subcellular evidence for the broad-spectrum resistance mediated by RPW8.2. RPW8.1 and RPW8.2 belong to a small gene family in the Arabidopsis and Brassica lineages. However, the cellular function of the other family members remains to be functionally characterized. Here, I report that all homologs of RPW8 (designated HR#) examined are EHM-residents, suggesting that the RPW8 family proteins share a common EHM-targeting signal. Moreover, through a reverse genetics approach I show that three Arabidopsis homologs, i.e. AtHR1, AtHR2 and AtHR3, appear to play a role in salicylic acid-dependent basal resistance against powdery mildew and perhaps other biotrophic pathogens. These results support our hypothesis that the two atypical resistance R genes, RPW8.1 and RPW8.2 evolved from duplication and functional diversification (enhancement) of a more ancient component of basal immunity in Arabidopsis (Chapter 2). Furthermore, I provide the first piece of cell biological evidence to suggest that the enigmatic EHM is formed via de novo synthesis rather than simple extension and differentiation of the host plasma membrane in the invaded host cell during the biogenesis of the fungal haustorium (Chapter 3). I also summarize my contribution to a project that aims to utilize RPW8 as a delivery vehicle to confer novel resistance in other crop species against a variety of fungal or oomycete haustorium-forming pathogens (Chapter 4) and ongoing efforts to further dissect the RPW8 defense and trafficking pathways in relation to bioactive phosphoinositides (Chapter 5) and to characterize putative interacting or signaling components of RPW8-mediated defense mechanisms against powdery mildew in Arabidopsis (Chapter 6).