Heart diseases resulting in heart failure are among the leading causes of morbidity and mortality in developed countries. The underlying molecular causes of cardiac dysfunction in most heart diseases are still largely unknown, but are likely to result from underlying alterations in gene and protein expression. Proteomics now allows us to examine global alterations in protein expression in the diseased heart and will provide new insights into cellular mechanisms involved in cardiac dysfunction and should also result in the generation of new diagnostic and therapeutic markers. In this article we review the current status of proteomic technologies and describe how these are being applied to studies of human heart disease.