The practice of medicine today is founded primarily on the phenotypic characteristics of diseases. The recognition of common forms of cardiomyopathies as hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathies typifies the phenotype-based approach to diseases. The approach clearly has had numerous positive impacts on the diagnosis, prognostication, prevention, and treatment of various diseases. The advent of the beta-blockers and inhibitors of the renin-angiotensin-aldosterone pathway in the treatment of systolic heart failure are testaments to the clinical utility of the phenotype-based approach. Despite the enormous impacts, however, the phenotype-based approach has considerable shortcomings. For example, the approach has failed to offer a cure for many diseases including systolic heart failure, in which pharmacologic interventions reduce mortality by approximately 20% to 30% and prolong survival by a few months (–3).