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During the last decades, the development of ever more powerful genetic, molecular and omic approaches has provided plant pathologists with a wide array of experimental tools for elucidating the intricacies of plant-pathogen interactions and proposing new control strategies. In the case of the Dutch elm disease (DED) pathosystem, these tools have been applied for advancing knowledge of the host (Ulmus spp.) and the causal agents (Ophiostoma ulmi, O. novo-ulmi and O. himal-ulmi). Genetic and molecular analyses have led to the identification, cloning and characterization of a few genes that contribute to parasitic fitness in the pathogens. Quantitative PCR and high-throughput methods, such as expressed sequence tag analysis, have been used for measuring gene expression and identifying subsets of elm genes that are differentially expressed in the presence of O. novo-ulmi. These analyses have also helped identify genes that were differentially expressed in DED fungi grown under defined experimental conditions. Until recently, however, functional analysis of the DED fungi was hampered by the lack of protocols for efficient gene knockout and by the unavailability of a full genome sequence. While the selective inactivation of Ophiostoma genes by insertional mutagenesis remains a challenge, an alternative approach based on RNA interference is now available for down-regulating the expression of targeted genes. In 2013, the genome sequences of O. ulmi and O. novo-ulmi were publicly released. The ongoing annotation of these genomes should spark a new wave of interest in the DED pathosystem, as it should lead to the formal identification of genes modulating parasitic fitness. A better understanding of DED, however, also requires that omic approaches are applied to the study of the other biotic components of this pathosystem.