Defined as the total cholesterol minus high-density lipoprotein (HDL), non-HDL cholesterol has been increasingly acknowledged as a measure of risk estimation for developing atherosclerotic cardiovascular diseases (ASCVD). Comprising of apolipoprotein B100-containing cholesterols (very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), and lipoprotein (a) (Lp(a))), and apolipoprotein B48-containing lipoproteins (chylomicrons and its remnants), elevated serum levels of non-HDL cholesterol in early adolescence has been strongly linked with the development of ASCVD in adulthood. This article reviews the evidence from longitudinal studies, which demonstrate the cumulative risk of ASCVD in relation to the elevated levels of non-HDL cholesterol earlier in life.