Background <p>γ-Glutamyltransferase (γ-GT) is a liver enzyme in glutathione metabolism and protects cells from oxidative stress. An isolated increase, in combination with normal other liver values, is a sensitive but non-specific marker for hepatobiliary diseases and chronic alcohol consumption.</p> Objectives <p>Etiology, differential diagnosis and clinical relevance of an isolated γ-GT elevation.</p> Materials and methods <p>The article summarises official statistics, case analyses, studies and expert recommendations and reclassifies them under the special aspect of isolated γ-GT elevation.</p> Results <p>Isolated γ-GT elevation is associated with a broader diagnostic spectrum, including various metabolic and cardiovascular diseases and an increased risk of mortality.</p> Conclusion <p>The interpretation of an isolated elevation in γ-GT requires a comprehensive evaluation of the medical history, physical examination, sonography and laboratory diagnostics. It is an important biomarker for prevention and diagnosis.</p>