Over the past several decades, it has been clearly established that higher plasma concentrations of high-density lipoprotein (HDL) are related to lower risk of coronary artery disease (CAD). According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, the HDL level of <40 mg/dL is considered low and is one of the CAD risk predictors. However, in the last decade, several studies have indicated the importance of the quality of HDL as another potential measure for CAD risk assessment. The loss of normal biological function of HDL particles as a result of multifactorial actions of chronic inflammation and acute phase responses has suggested a new potential pathway in the pathophysiology of atherosclerosis. The concept of "dysfunctional HDL" or "proinflammatory HDL," which exhibits chameleon-like properties of converting a positive force protecting arteries to a negative one, enhancing atherogenesis is now under active investigation. Measurements of this dysfunctional quality of HDL in cell-based or cell-free assays by analyzing anti-inflammatory functions may link these changes to in vivo assessments of vascular disease. This review provides details on functional and dysfunctional HDL and summarizes recent studies into dysfunctional HDL and its potential links to CAD.