Natural polyamines - putrescine, spermidine and spermine - are aliphatic polycations occurring in all living cells. Here they can bind nucleic acids and proteins, and modulate gene expression and intracellular signalling cascades. Polyamines are essential factors for eukaryotic cells: deregulation of their biochemical pathway is an established player in tumour promotion and progression. Several studies, from our and other laboratories, also pointed at their role in the heart in a variety of experimental models ranging from cell cultures to whole animals. Accumulating evidence indicates that polyamine metabolism is involved in cardiac cellular growth, functioning and death. A specific set where it appears to be relevant is the hypertrophic hearth muscle, adapting to both physiological (e.g. chronic exercise) and pathophysiological (e. g. chronic hypertension) stimuli with the aim to increase ventricular pump function and to decrease cardiac wall tension. Individual myocyte growth sustains the hypertrophic phenotype at the cellular level, where gene transcription and protein synthesis are typical features, both known to be promoted by polyamines. Indeed, their increased concentrations were reported in the heart after ascending aortic stenosis, stress or physical exercise, or administration of the beta-adrenoceptor agonist isoproterenol (ISO) - all inducers of cardiac hypertrophy. This rise in cellular polyamine content is consistent with histone hyperacetylation, and elevated RNA and protein synthesis. Conversely, inhibition of ornithine decarboxylase (ODC), the first enzyme of polyamine metabolism, reduces polyamine content and attenuates ISO- and clenbuterol-induced cardiac hypertrophy. A number of transgenic and knockout mouse models, with altered levels of polyamine-metabolizing enzyme are today available. The targeted overexpression of ODC to the heart produces baseline cardiac hypertrophy. Beta-adrenergic stimulation with ISO increases the left ventricular hypertrophy in these transgenic mice. ISO also induces arginase activity in these transgenic hearts. Arginase catalyzes the conversion of arginine to ornithine, the ODC substrate. On the other hand, arginine is also the substrate for nitric oxide synthases (NOS), which lead to the synthesis of nitric oxide (NO). Reduced levels of NO are consistent with development of cardiac hypertrophy, and NOS overexpression was shown to attenuate the hypertrophic effect of ISO. Moreover, NO can inhibit ODC activity and reduce polyamine content, and polyamines can inhibit NOS. All these evidences point at arginase, NOS and ODC as candidate players in a biochemical network modulating cardiac remodelling.