Modern concept in primary prevention of cardiovascular diseases (CVD) entails assessing the person's global risk and making the right management in accordance with these results. Correspondingly, 3 steps recommended for the prevention of CVD under risk guidance are: (a) risk assessment via a proper system like Framingham Risk Score, SCORE, QRISK, PROCAM; (b) decision-making in the proper management in terms of informing the patient about lifestyle changes that he or she can cope and drug selection; and (c) evaluation of treatment decision in terms of cost effectiveness. Although, a significant decline is observed in CVD morbidity and mortality, particularly in the western countries, we still are trying to approach to competent quality measures about management under CV risk guidance. This review summarizes the main challenges regarding risk stratification-guided management strategy in primary prevention of CVD.