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Blood folate concentration is decreased by tobacco smoking and presumably secondhand smoke. Because low folate concentration is associated with hyperhomocysteinemia, both are emerging as important and independent risk factors for atherosclerosis as well as prediction of early coronary artery disease. The primary cause of low folate concentration in smokers might be related to lifestyle and dietary habits. Smokers tend to consume fewer folate-rich fruits and vegetables vs non-smokers. Adverse cardiovascular health is generally attributed to toxic gases, particulates, and tars generated from tobacco smoking. Although low folate concentration and hyperhomocysteinemia are typically found in smokers, their role in this pathophysiologic process remains controversial. In fact, several studies failed to demonstrate a beneficial effect of daily folic acid supplementation as a homocysteine-lowering therapy on cardiovascular outcome even in smokers. In this review, we investigate the relationship between folate status and smoking.