Low density lipoprotein cholesterol (LDL-C) reduction leads to significant decreases in coronary events, as well as in most large trials performed recently, cardiovascular and total mortality. The lowest risk of coronary events occurs among people with the lowest LDL-C levels. Achieving a target LDL-C level less than 2.5 mM in individuals at high risk of a coronary event often necessitates the use of lipid-lowering drugs, primarily statins. Review of the major clinical trials involving statins reveals that LDL-C reduction is associated with a significant reduction in coronary events in men and women, older individuals, those with various other risk factors and those with either coronary artery disease or a high risk of developing it. The greatest clinical benefits have been associated with the greatest LDL-C reductions, although the incremental benefit is less at lower levels. Ongoing studies will help determine optimal new treatment targets for LDL-C.