Proteomics studies have extended the list of identified apolipoproteins and associated proteins present in HDL and its subclasses. These proteins appear to cluster around specific functions related to lipid metabolism, inflammation, the immune system, hormone-binding, hemostasis, and antioxidant properties. Small studies suggest that there are substantial differences between the HDL proteome from cardiovascular disease patients and that from controls. Furthermore, dyslipidemia therapy shifts the HDL proteome from patients toward the profile observed in healthy controls. In addition, the proteome of HDL and LDL from patients with insulin resistance and peripheral atherosclerosis show significant differences with that of matched healthy controls. The proteome of HDL and LDL density subclasses have apolipoproteins and associated proteins profiles that suggest subclass-specific functions. However, proteomics studies of lipoproteins are few and small and should be interpreted with caution. Nonetheless rapid technical progress in proteomic platforms suggest that soon analysis time will be reduced and precise measurement of identified proteins will be possible. This, combined with controlled purification steps of HDL and its subclasses should provide further information about proteins involved in the particles postulated spectrum of functions, including those believed to be atheroprotective.