Although the past 4 decades have been the most productive in transitioning from an low-density lipoprotein cholesterol (LDL-C) hypothesis to demonstration of clinical benefit, cardiovascular disease remains a major cause of mortality and morbidity. It is fortunate that most of the effective lipid-lowering drugs, the statins, have become generic and inexpensive. However, there remains a large unmet medical need for new and effective agents that are also well tolerated and safe, especially for patients unable to either tolerate statins or achieve optimal LDL-C on current therapies. It is likely that the agents discussed in this review will fill that need.