Abstract Alcohol abuse is a major cause of abnormal liver function throughout the world. While measurements of liver enzyme activities (GGT, ALT, AST) are important screening tools for detecting liver disease, due to lack of ethanol-specificity and inconsistencies regarding the definitions of significant alcohol consumption, several other blood tests are usually needed to exclude competing and co-existing causes of abnormal liver function. Information on the specific role of ethanol consumption behind hepatotoxicity may be obtained through measurements of blood ethanol and its specific metabolites (ethyl glucuronide, phosphatidylethanol, protein-acetaldehyde condensates and associated autoimmune responses). Recent studies have indicated that being overweight is another increasingly common cause of abnormal liver enzyme levels and adiposity may also increase the impact of ethanol consumption on liver pathology. Interestingly, increased liver enzyme activities in circulation may reflect not only hepatic function but can also serve as indicators of general health and the status of oxidative stress in vivo. ALT and GGT activities predict insulin resistance, metabolic syndrome, mortality from coronary heart diseases and even mortality from all causes. If the upper reference limits for liver enzyme activities were defined based on the data obtained from normal weight abstainers, the clinical value of liver enzyme measurements as screening tools and in patient follow-up could be significantly improved.