The presence of calcification in atherosclerotic arteries has long been recognized, but the mechanisms of calcification remain poorly understood. Risk factors of atherosclerosis, such as age, sex, hyperlipidemia, diabetes mellitus, hypertension, left ventricular hypertrophy, and smoking, have been shown to predict future coronary events. Traditionally, parameters known to be of predictive value were included in conventional risk scores such as the Framingham risk score 1 and helped to divide patients into high risk, intermediate risk, and low risk of future cardiovascular events. 2 Also, many studies have shown that calcification is accelerated in the presence of diabetes mellitus and chronic renal failure. 3–5 Since the introduction of computed tomography (CT), a noninvasive technology with the ability to not only determine the extent of coronary narrowing but also determine the extent of vessel wall thickening, remodeling, and, above all, the presence or absence of calcification was lacking. Agatston et al 6 devised a coronary artery calcification (CAC) scoring scheme, and others have shown calcium score to be a better predictor of future events than the Framingham risk index alone. 7 There is also a close relationship between the presence of CAC and atherosclerotic plaque burden, with angiographic studies showing high sensitivity but poor specificity of CAC score for predicting obstructive disease. 8 Physical activity is known to decrease cardiovascular mortality; however, there is no relationship between the extent of coronary calcification as assessed by CT in individuals engaged in moderate exercise. 9 Allison et al 10 showed that calcification in different vascular bed was predictive of different outcomes. Coronary calcification was predictive of cardiovascular disease mortality, whereas calcification in thoracic aorta, carotid arteries, and iliac arteries were predictive of total mortality when followed for 7.8 years. 10 At the same time, histopathologic studies indicate that heavily calcified plaques are stable plaques and unlikely to lead to coronary events, whereas the vulnerable plaque tends to be either noncalcified or with only mild to moderate calcification, suggesting that calcification may exert a protective effect. 11 These studies indicate that calcification is a complex, organized, and highly regulated process. Demer and Tintut 12 have suggested that we divide calcification into 3 categories, that is, inflammatory (atherosclerotic, mostly intimal), metabolic (chronic kidney disease [CKD] and diabetes mellitus, mostly medial), and genetic background (pseudoxanthoma elasticum, generalized arterial calcification of infancy, arterial calcifications attributable to deficiency in CD73, and Marfan syndrome, mostly medial), although admitting that this may be an oversimplification. We will discuss the mechanisms of intimal atherosclerotic and valvular calcification, as well as calcification secondary to metabolic disorders because of some similarity in risk factors and clinical relevance.