Oomycetes, such as Phytophthora, downy mildew causal agents, and Pythium, form a unique branch of eukaryotic-plant pathogens with an independent evolutionary history. Among the oomycetes, Phytophthora spp. cause some of the most destructive plant diseases in the world, and are arguably the most devastating pathogens of dicotyledonous plants. Large scale DNA sequencing (genomics) approaches promise to impact Our understanding of the molecular basis of pathogenicity and host specificity in Phytophthora by facilitating the isolation of novel virulence and avirulence genes, as well as by helping to identify targets for chemical control. Structural genomic studies of Phytophthora are well under way. The challenge in the postgenome era is to link a sequence to a phenotype with as little experimental effort as possible, using computational tools for data mining and robust high throughput functional assays. In this article, we review our strategy of applying a sequence-to-phenotype (or functional genomics) paradigm to the discovery of novel virulence and avirulence genes, as well as the identification of novel fungicide targets in Phytophthora.