Cigarette smoking is a major risk factor for development of cardiovascular disease and stroke. Nicotine is the addictive component in tobacco smoke. Currently, nicotine supplements such as nicotine patches, nasal spray, inhaler and gum are used in smoking cessation. In addition, nicotine treatment is being investigated in other diseases such as acute ulcerative colitis, sleep apnea, Parkinson’s and Alzheimer’s disease. Given the potential broad therapeutic uses of nicotine, there is a need to understand how nicotine affects the cardiovascular system independent of smoking. Nicotine affects the cardiovascular system through direct and indirect mechanisms. Direct mechanisms include stimulation of autonomic neurons, which innervate the heart and blood vessels. Nicotine also directly affects components of the vascular wall including release of vasoactive and mitogenic factors from the vascular endothelium and smooth muscle. Nicotine indirectly affects vascular function through alterations in circulating catecholamines released from the adrenal glands and profile of circulating lipids. Data derived from subacute administration of nicotine to experimental animals and humans suggests that in concentarions used clinically for smoking cessation and other disorders, nicotine would not increase the risk of cardiovascular disease.