BACKGROUND A wide variety of pathological conditions have been shown to result in cardiac remodelling and myocardial dysfunction. However, the mechanisms of transition from adaptive to maladaptive alterations, as well as those for changes in cardiac performance leading to heart failure, are poorly understood. METHODS Extensive studies have revealed a broad spectrum of progressive changes in subcellular structures and function, as well as in signal transduction and metabolism in the heart, among different cardiovascular disorders. The present review is focused on identifying the alterations in molecular and biochemical structure of myofibrils (myofibrillar remodelling) in hypertrophied and failing myocardium in different types of heart diseases. Numerous changes at the level of gene expression for both contractile and regulatory proteins have already been reported in failing hearts and heart diseases; these changes are potential precursors for heart failure such as cardiac hypertrophy and cardiomyopathies. Myofibrillar remodelling, as a consequence of proteolysis, oxidation, and phosphorylation of some functional groups in both contractile and regulatory proteins in hearts failing due to different etiologies, has also been described. CONCLUSIONS Although myofibrillar remodelling appears to be associated with cardiac dysfunction, alterations in both contractile and regulatory proteins are dependent on the type and stage of heart disease.