Alcoholism ranks as one of the main current threats to the health and safety of people in most Western countries. Therefore, a high priority should be given to aims at reducing its prevalence through more effective diagnosis and early intervention. The need for objective methods for revealing alcohol abuse in its early phase has also been widely acknowledged. It is postulated here that the diagnosis of alcohol use disorders could be markedly improved by a more systematic use of specific questionnaires and laboratory tests, including blood ethanol, serum gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mean corpuscular volume of erythrocytes (MCV). Recent research has provided new insights into the relationships between ethanol intake, biomarkers, and factors affecting their diagnostic validation, including gender, age, and the effects of moderate drinking and obesity. It appears that the concept of reference intervals for several ethanol-sensitive parameters in laboratory medicine needs to be revisited. CDT is currently the most specific marker of alcohol abuse, and when combined with GGT using a mathematically formulated equation a high sensitivity is reached without loss of assay specificity. Possible new biomarkers include minor ethanol metabolites (protein-acetaldehyde condensates and associated autoimmune responses, ethylglucuronide, and phosphatidylethanolamine), 5-hydroxytryptophol, and genetic markers although so far their routine applications have been limited.