The traditional concept of ‘higher the better’ for high-density lipoprotein cholesterol (HDL) has been challenged. Contemporary data demonstrates a ‘U-shaped’ association between HDL-C and clinical outcomes. These observations suggest that extremely low and high level of HDL-C is hazardous and the quality of HDL is more important than quantity.  Focus has shifted from HDL-C level as a biomarker to the measurement of HDL function. Mechanism of this unique paradoxical association remains elusive. Investigating novel therapeutic agents to improve HDL functions, measured through cholesterol efflux capacity (CEC) or HDL inflammatory index (HII), will be critical for translation of HDLs from diagnostic to therapeutic targets and will offer an exciting arena for future research. Until then, physicians should remain cognizant that HDL may not always be good cholesterol and HDL-C levels should always be interpreted in the context of concomitant lipid abnormalities and other modifiable risk factors. “Not enough to have a lot of HDL — what matters is how that HDL functions.”