This article will discuss our current understanding of the role of HDL-C in the statin era, focusing on the question as to whether HDL-C still "counts" when determining cardiovascular risk. Epidemiologic evidence consistently demonstrates that low HDL-C is a strong and independent risk factor for CHD. The epidemiologic evidence is complimented by clinical data showing that interventions that raise HDL-C are associated with reductions in CHD risk, as well as by a growing body of experimental data demonstrating biologically plausible mechanisms that may underlie the observed clinical findings. Analyses of large statin trials also indicate that the significant and independent relationship between HDL-C and CHD risk persists despite the therapeutic effects of statins, and that HDL-C levels in statin-treated patients, both at baseline and in response to statin therapy, are relevant. Early studies on novel HDL targeting therapies are promising, but their long term safety profile and impact on clinical outcomes is yet to be determined in larger studies. Recent guidelines emphasize low HDL-C as an independent risk factor for cardiovascular disease, specifically identify HDL-C as a target for intervention, and encourage the use of HDL-C raising interventions in high-risk patients with low HDL-C levels.