This chapter describes the use of denaturing high-performance liquid chromatography as a high-throughput method to detect genetic mutations in pediatric cardiomyopathies. An overview of the classification, incidence, and etiologies of the major cardiomyopathies is provided, with emphasis on the special circumstances of the pediatric patient. During the past 15 yr, the genetic bases of inherited dilated, hypertrophic, and restrictive cardiomyopathy have been elucidated. As the list of known and candidate cardiomyopathy genes continues to grow and our ability to screen for genetic mutations improves, the cause of cardiomyopathy will be identified in a larger percentage of cases. This outcome is highly relevant to children with cardiomyopathy as well as those at risk for developing the disease because of their family history.