High density lipoprotein (HDL) is protective against atherosclerosis through multiple functions, including mediating reverse cholesterol transport, anti-oxidation, anti-inflammation, and endothelial protection. However, in the state of inflammation and metabolic diseases, due to alteration, oxidation or modification of HDL composition, HDL particles can be transformed into proatherosclerotic “dysfunctional” HDL, which is associated with an increased incidence of cardiovascular events. This paper reviews the composition and functional characteristics of dysfunctional HDL in order to provide new diagnostic and therapeutic approaches for atherosclerotic cardiovascular disease.