A large proportion of the United States population requires aggressive low-density lipoprotein (LDL) cholesterol- lowering therapy to meet the new treatment guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. This has further widened the gap between the number of people being treated compared with those who should be treated. Moreover, many people being treated do not meet their LDL cholesterol goal. Diet and healthy lifestyle practices remain the cornerstone of treatment to lower LDL cholesterol. Pharmacologic therapy has assumed an increasingly important role in reaching LDL cholesterol goals. Diet and healthy-lifestyle interventions have been shown to augment the benefits of cholesterol-lowering drugs. Together, this dynamic duo provides the most effective clinical means identified to date for maximally lowering LDL cholesterol levels.