Genomics and proteomics are becoming powerful tools for profiling diseased states. The human genome is estimated to encode 30,000 to 40,000 genes, generating more than 100,000 functionally distinct proteins. Microarray data are available for multiple models of heart disease as well as for diseased and failing human hearts. Similarly, two-dimensional gel data banks of normal and diseased myocardium from multiple species are published and are available on the Internet. The combined technologies are beginning to provide new insights into the causes and pathways of cardiac dysfunction. This article reviews the novel findings that have been acquired from genomic and proteomic screens of diseased hearts in animal models and humans.