The last 50 years have experienced a rapid evolution in the development of lipid-lowering agents to reduce low-density lipoprotein cholesterol levels. This significant advance in medicine has not occurred without debate. Whether lowering blood cholesterol levels was beneficial has remained one of the most controversial issues during the past 50 years. The discovery of statins was the revolution that made it possible to delay and stop the progression of the atherosclerotic process resulting in improved health and longevity for millions of people. To date, statins remain the drugs of choice for the treatment of hypercholesterolemia. Despite their use, the risk of cardiovascular events persists. Therefore, the use of non-statin drugs, such as ezetimibe or PCSK9 inhibitors, in combination with statins has been shown to further reduce the risk of cardiovascular events. This review aims to summarize the advances in the field of lipid-lowering therapies over the past 50 years, focusing on advances in the development of drug therapies up to and including gene silencing or gene editing treatments that are expected in the near future.