Cardiovascular epidemiology has recently highlighted a clear link between serum gamma-glutamyltransferase (GGT) and risk for stroke, infarction and cardiovascular death, associated with the evolution of atherosclerosis-related conditions, such as coronary artery and cerebrovascular disease. Thus, serum GGT is now recognized as a cardiovascular prognostic marker. However, the reasons for the association between serum GGT elevations and unfavorable prognosis remain to be defined. Histochemistry and biochemistry have provided intriguing clues, focusing new research approaches on the complex issue of monitoring and treatment of chronic cardiovascular conditions.