Gamma-glutamyltransferase (GGT), regarded as a marker of excessive alcohol consumption or liver disturbances, is an enzyme catalyzing the first step in the extracellular degradation of the antioxidant glutathione (GSH) and may take part in atherogenesis. The marked relationship between GGT and the atherosclerotic process has shifted attention to the issue of whether its serum levels can aid in the detection of individuals at high risk for incident cardiovascular events. It is likely that the process entails the oxidation of low-density lipoprotein through GSH/GGT-dependent iron reduction within the plaque. In this context, oxidative stress is a probable mediator. Recent insights into the pathophysiological background of GGT in the precipitation and progression of atherosclerosis appear to be supported by relevant epidemiological observations as a cardiovascular risk predictor. Further understanding is, nevertheless, warranted to ameliorate the prognostic stratification of patients through GGT.