<p>Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide. Over the last two decades, different risk score models, generally assessing the short-term (10-year) risk estimates, have been developed to predict risk and to provide guidance for informed decision-making regarding initiation or intensification of CVD prevention strategies. However, the short-term risk estimation of CVD mortality/morbidity deeply underestimates the lifetime CVD risk, especially in younger age individuals and in women. Moreover, the greatest number of CV events occurs in subjects with low/moderate short-term risk because they are prevalent in the general population. By contrast, estimates of the lifetime risk of CVD may provide a more comprehensive assessment by considering both traditional and non-traditional CV risk factors as well as the potential competing risks, which leads to a more accurate and tailored assessment of the patient’s health status. Aim of the present manuscript is to review the latest proposed strategies regarding the estimation of lifetime CV risk and how these strategies may be helpful in daily clinical practice both in primary and secondary prevention.</p>