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Although rapid growth of the heart during early postnatal development ceases with maturation of the organism, the potential for cardiomyocyte growth is not lost and may be observed even in senescent hearts. Rapid developmental heart growth is accompanied by a proportional growth of capillaries but not always of larger vessels, and thus coronary vascular resistance gradually increases. Growth of adult hearts can be enhanced by thyroid hormones, catecholamines and the renin-angiotensin system hormones, but these do not always stimulate growth of coronary vessels. Likewise, chronic exposure to hypoxia leads to growth, mainly of the right ventricle and its vessels but without vascular growth elsewhere in the heart. On the other hand, ischaemia is a potent stimulus for the release of various growth factors involved in the development of collateral circulation. Heart hypertrophy develops in response to training, pressure or volume overload. Training usually leads to growth of larger coronary vessels but little growth of capillaries, except in young animals. However, growth of the capillary bed, but not the resistance vasculature capacity, can be induced by either increased coronary blood flow, bradycardia (electrically or pharmacologically induced) or increased inotropism, all of which are involved in the training stimulus. Thus, what actually promotes growth of larger vessels as opposed to capillaries in training is unclear. Pressure overload hypertrophy is mediated by both the renin-angiotensin system and the response of cardiomyocytes to stretch; both lead to activation of early oncogenes (c-fos, c-jun, c-myc) and angiotensin II activates several protein kinases involved in cell growth. In this condition, growth of larger vessels is inadequate, although some capillary growth may occur. Volume overload leads to cardiomyocyte hypertrophy and hyperplasia and some increase in vascular supply. Deficits in capillary supply in pressure or volume overload hypertrophy can be reversed by chronic administration of ACE inhibitors, dipyridamole, the bradycardic drug alinidine or pacing-induced bradycardia respectively, but in neither case is training effective. Mechanical and humoral factors are involved in growth of cardiomyocytes and vessels. For cardiomyocytes, stretch is most important, activating oncogenes, protein kinases and possibly the inositol phosphate pathway, but not ion channels, with regulation by the balance of angiotensin II, TGF-beta 1 and IGF-1, but not FGFs. For vessels, growth is stimulated by stretch and shear stress, possibly with involvement of VEGF. Increased shear stress disrupts the glycocalyx on the luminal side of vessels and releases plasminogen activator and metalloproteinases which disrupt the basement membrane and enable endothelial cell migration and proliferation. It also causes rearrangement of the endothelial cytoskeleton and transmission of mechanical signals to the abluminal side disturbing extracellular matrix and causing distortion of capillary basement membrane. Stretch acting from the abluminal side has a similar effect resulting also in basement membrane disruption and endothelial cell proliferation.