Metallothioneins (MTs) discovered four decades ago as metal binding low molecular weight thiol proteins, in recent years, have generated immense interest due to their involvement in various physiological and pathophysiological events. In spite of the recent advances in the knowledge base in MTs, no specific study on the isolation or characterization of MTs isoforms and their precise function in the heart has been conducted. Although most stress conditions in the heart do not produce much change in myocardial MTs, TNF-alpha and IL-6 do induce MT in the heart to the extent comparable with the liver. Cardiotoxicity of anticancer drugs and vulnerability of the heart to other oxidative stress conditions may partially be due to lack of inducibility of MT in the heart by these interventions. A clear understanding of induction of MTs in the heart may help in the development of better approaches to modulate the pathogenesis of cardiomyopathies and heart failure.