The pathogenic mechanisms underlying cardiac dysfunction in heart disease are still largely unknown. It is likely, though, that significant alterations in myocardial gene and protein expression underlie these disease processes and determine their progression and outcome. Most molecular studies of cardiac dysfunction have been carried out on specific cellular systems. However, the application of the proteomic approach to the study of heart disease has made it possible to characterize global alterations in protein expression. This promises new insights into the cellular mechanisms involved in cardiac dysfunction and is likely to result in the discovery of novel diagnostic markers and new therapeutic opportunities.