Lipid-modifying therapy has been proven to significantly reduce cardiovascular events and total mortality. Most of the data have come from statin trials. Statin therapy is generally well-tolerated and safe, and for patients who are at higher than average risk of cardiovascular disease, the benefit of lipid-modifying therapy far exceeds the risk. Careful risk assessment is a critical component of effective lipid-modifying therapy. In the foreseeable future, low-density lipoprotein cholesterol (LDL-C) will remain the primary therapeutic target, and combination therapy is likely to become the norm. The major questions are how low to treat and how to achieve increasingly aggressive targets in lipid-lowering therapy. Many patients on LDL-lowering therapy continue to have abnormalities of the triglyceride–high-density lipoprotein (TG-HDL) axis, so additional drug therapy is often considered for such patients. In this review, we briefly discuss new developments in cardiovascular risk assessment, then discuss recent developments in treatment to reduce LDL, and finally discuss current concepts regarding therapy targeting the TG-HDL axis.