Abnormal liver enzymes may be present in the absence of symptoms and signs of liver disease. A good clinical history and physical examination are mandatory. If a systematic approach is adopted, based on additional non-invasive serological tests and imaging procedures covering the most frequent liver diseases, the cause is often apparent. The clinician should be aware of nonhepatic diseases that can cause abnormal liver enzymes, such as thyroid disorders and occult celiac disease. In those patients in which no explanation can be found at the time of the initial evaluation for these abnormal liver enzymes, there is a high probability of non-alcoholic fatty liver disease. The risks and benefits of a liver biopsy in this setting should be carefully considered, as it only seldom alters management.