Elevated low-density lipoprotein cholesterol (LDL-C) is an established cause of cardiovascular disease and subsequent adverse events. The efficacy and safety of lowering plasma LDL-C to reduce the risk of coronary heart disease (CHD) and secondary event rates are now well established. What has not been established, however, is a plasma LDL-C lower threshold level of safety and efficacy. Here we review intensive plasma LDL-C-lowering with statins and argue that even further reductions of plasma LDL-C than current guideline targets is likely to safely reduce cardiovascular event rates. We discuss how to achieve very low levels of plasma LDL-C using both traditional and novel LDL-lowering therapies.