Several cross-sectional studies have reported a relationship between elevated serum activity of liver enzymes [e.g. alanine aminotransferase (ALT) and gamma-glutamyltransferase (γGT)] and metabolic syndrome (MetS) and/or diabetes mellitus (DM). Raised serum activity of liver enzymes independently predicted the future development of MetS and DM as well as cardiovascular (CV) events and/or total/CV mortality in prospective studies. However, this association was not consistently demonstrated and it appears to be independent of alcohol intake. Even though these associations can be partly attributed to non-alcoholic fatty liver disease (NAFLD) and insulin resistance, there may be additional underlying mechanisms that contribute to the increased CV risk (e.g. inflammation and oxidative stress). The association of γGT with atherosclerotic plaque is of particular importance.