Both growth hormone (GH) and insulin-like growth factor I (IGF-I) are involved in heart development and in maintenance of cardiac structure and performance. Cardiovascular disease has been reported to reduce life expectancy in both GH deficiency (GHD) and GH excess. Patients with GHD suffer from a cluster of abnormalities associated with increased cardiovascular risk, including abnormal body composition, unfavorable lipid profile, increased fibrinogen and C-reactive protein levels, insulin resistance, early atherosclerosis and endothelial dysfunction, and impaired left ventricular (LV) performance (i.e., reduced diastolic filling and impaired response to peak exercise). Long-term GH replacement therapy reverses most of these abnormalities. More consistently, GH replacement reduces body fat and visceral adipose tissue, reduces low-density lipoprotein cholesterol and triglyceride levels, and improves endothelial function. GH replacement also reduces intima media thickness at major arteries and improves LV performance, but these results have been observed only in small series of patients treated on a short-term basis. This review discusses the roles of GHD and GH replacement therapy in the development of cardiovascular disease.