The use of pharmacological lipid-lowering intervention in individuals with hypercholesterolaemia and known cardiovascular disease or diabetes/chronic kidney disease is well established. Current European Society of Cardiology guidelines recommend immediate initiation of drugs in adjunct to lifestyle intervention in these patients at high or very high cardiovascular risk. In these clinical settings, statins are generally chosen as the first-choice drug intervention, in consideration of the robust evidence showing a reduction in all-cause mortality and major adverse cardiac events (MACE). In contrast, primary prevention with statins, even in the subset of patients at high-risk of cardiovascular events, is not well implemented. This might be related to a lack of public awareness regarding the actual risk associated with prolonged exposure to high concentrations of low-density lipoprotein cholesterol (LDL-C) and uncertainties in the clinical evidence coming from the earliest trials in this patient subset. However, recent observational studies suggest that lowering LDL-C earlier in life and for a longer duration can substantially decrease the burden of cardiovascular disease and mortality. Moreover, results from recent well-conducted large meta-analyses of randomized clinical trials showed that primary prevention with statins reduced all-cause mortality by 14% and MACE by > 20% - findings similar to those observed for the use of statins in secondary prevention. Recently published American Heart Association/American College of Cardiology guidelines on the treatment of blood cholesterol emphasize that primary prevention using high-dose statins in individuals with LDL-C ≥ 190 mg/dL induces a benefit in atherosclerotic cardiovascular risk reduction that clearly exceeds the potential for adverse effects. We aim in this review to discuss the new data that advocate the use of statins in primary prevention earlier and more frequently, putting the efficacy evidence into perspective with new insights in terms of safety issues.