High density lipoproteins (HDL) are heterogeneous lipoproteins, the HDL subclass exhibits different atherosclerotic protective effects and cardiovascular protection. The distribution of HDL subclasses also changes dynamically with age, gender, etc. Drugs that affect HDL function and subclass distribution may be more effective ways to protect from cardiovascular risk. This article reviews the detection of HDL subclasses, anti-atherosclerotic function and its association with cardiovascular disease, and provides a new perspective for the prevention and treatment of cardiovascular diseases in humans.