The fruit fly, Drosophila melanogaster , has been used to study genetics, development, and signaling for nearly a century, but only over the past few decades has this tremendous resource been the focus of cardiovascular research. Fly genetics offers sophisticated transgenic systems, molecularly defined genomic deficiencies, genome-wide transgenic RNAi lines, and numerous curated mutants to perform genetic screens. As a genetically tractable model, the fly facilitates gene discovery and can complement mammalian models of disease. The circulatory system in the fly comprises well-defined sets of cardiomyocytes, and methodological advances have permitted accurate characterization of cardiac morphology and function. Thus, fly genetics and genomics offer new approaches for gene discovery of adult cardiac phenotypes to identify evolutionarily conserved molecular signals that drive cardiovascular disease.