With the availability of the entire genome of the model tree Populus trichocarpa Torr. & A. Gray and the current genome sequencing project of its rust pathogen Melampsora larici-populina Kleb., rust–poplar interaction research has entered the genomic era. Recent genomics research on poplars has attempted to connect the genetic localizations of loci for qualitative and quantitative disease resistance with putative genes encoding resistance or signalling proteins. The interactions between these putative resistance genes and rust effectors remain unknown. Genomic resources developed for Melampsora spp. promise to contribute to our understanding of the molecular basis of pathogenicity by facilitating the isolation of pathogenicity genes. A multifaceted approach for the identification of such genes that relies largely on trimming and sequence data analysis has been developed. The strategy takes advantage of the resources available and combines EST libraries, bioinformatics data mining for extracellularly expressed secreted proteins, intra- and inter-specific comparative genomics, and testing for the presence of positive selection. It has resulted in the discovery of several putative candidate genes. In silico evidence for candidate genes will be further validated by robust experimental evidence through functional analyses.