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Despite optimally reducing low-density lipoprotein cholesterol (LDL-C) levels to recommended targets using intensive statin therapy, the risk of cardiovascular disease (CVD) remains significant. Low levels of high-density lipoprotein cholesterol (HDL-C; <1.03 mmol/l or <40 mg/dl) are an independent risk factor for CVD, and raising levels of HDL-C is a major treatment strategy for regressing atherosclerosis and enhancing CVD risk reduction. This can be achieved by both nonpharmacological lifestyle measures and pharmacological treatment strategies.This article will focus on the currently available and emerging pharmacological treatment strategies for raising HDL-C. Extended-release nicotinic acid (or Niacin) remains the most effective pharmacological treatment currently available for elevating HDL-C, having recently been combined with simvastatin (as Simcor) and laropripant (as Cordaptive, to reduce flushing). Other HDL-C-raising agents in current clinical use or in clinical development are fibrates, peroxisome proliferator-activated receptor agonists, cholesteryl ester transfer protein inhibitors, and HDL-C mimetics. Novel pharmacological targets for raising HDL-C also include the nuclear liver X and farnesoid X receptors and endothelial lipase.Novel well tolerated and efficacious treatment strategies for raising HDL-C are required to target atherosclerosis and enhance CVD risk reduction.