The association between low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and the development of coronary heart disease (CHD) is well established. The management of CHD has traditionally focused on the reduction of LDL cholesterol or on the total lipid profile. Yet, treatment strategies for reducing risk in CHD also requires a focus on increasing low HDL cholesterol, as LDL cholesterol reduction alone is insufficient in preventing CHD events. This article reviews the strategies for targeting HDL cholesterol to optimize outcomes in CHD.