Cardiomyopathies are diseases of the heart resulting in impaired cardiac muscle function, which can lead to heart dilation or overt heart failure. These diseases represent a major cause of global morbidity and death. Innovative preventive and therapeutic measures are urgently needed for early detection, categorization, and treatment of patients at risk of cardiomyopathy. These developments will require a more complete understanding of the molecular effects of impaired cardiac function, even prior to overt disease. The use of gel-free expression proteomics in the detailed analysis of cardiac tissues should yield significant insight into the pathophysiology of these diseases.