Pseudoperonospora cubensis and Phytophthora capsici are plant pathogenic oomycetes that are severe threats to cucurbit cultivation because of the their global distribution, their broad host range among the Cucurbitaceae family, and their ability to overcome susceptibilities to host, environment, and chemical management. Historically, these pathogens have been extensively studied in terms of their life cycles and infection strategies in order to determine appropriate methods to manage disease. In recent years, the genomes of both pathogens have been sequenced, which will lead to greater opportunities for pathogen detection and will help researchers to better understand the host-pathogen interaction. In Ps. cubensis, the transcriptomes of both Ps. cubensis and Cucumis sativus (cucumber) have been sequenced, and this data is being analyzed to determine the function of Ps. cubensis effectors and the role of alternative splicing in the regulation of pathogen gene expression. Previous and ongoing work is being done to determine cucumber genes involved in resistance. In P. capsici, effectors have been identified in the genome sequence, and the genome being used to identify variation in different P. capsici isolates. Future work is needed to give biological meaning to genomics data and to determine mechanisms of pathogenicity in oomycetes and resistance in cucurbits. Herein, we will present an overview of the current and future objectives of genome-based research in this area, describing the molecular mechanisms of pathogen virulence and host response to infection.