Randomized clinical trials have demonstrated that increasingly intensive lowering of low-density lipoprotein cholesterol (LDL-C) reduces the rate of cardiovascular events in the primary and secondary prevention setting. Integration of serial coronary imaging within clinical trials has enabled evaluation of medical therapies on the natural history of coronary disease. These studies have extended from early investigation of coronary obstruction with angiography to more contemporary evaluation of plaque burden and composition with imaging modalities that directly visualize the artery wall. The findings of these trials have demonstrated that intensive lipid lowering promotes plaque regression and stabilization. The lessons of this body of research provide a biological rationale underscoring the ability of intensive lipid lowering to reduce cardiovascular risk and have the potential to promote greater uptake in clinical practice. Display omitted •Intensive lipid lowering with statin monotherapy or combination therapy is achievable in most high risk patients.•Intensive lipid lowering slows progression of obstructive disease on coronary angiography.•Intensive lipid lowering promotes plaque regression and stabilization, proportional to LDL-C lowering.•These benefits are likely to underscore the impact of intensive lipid lowering on cardiovascular risk.