High-throughput studies have enabled the large-scale mapping of synthetic lethal genetic interaction networks in the budding yeast Saccharomyces cerevisiae (S. cerevisiae). Recently, complementary high-throughput methods have been developed to map genetic interactions in the fission yeast Schizosaccharomyces pombe (S. pombe), enabling comparative analyses of genetic interaction networks between S. pombe and S. cerevisiae, two species separated by hundreds of millions of years of evolution. The resultant data has providing our first view of a possible core genetic interaction network shared between two distantly related eukaryotes, and identified numerous species-specific interactions that may contribute to the unique biology of these two different organisms. These and other results suggest that comparative interactomic studies will provide novel insights into the structure of genetic interaction networks.