Approximately 10% to 20% of the general population has elevated liver chemistry levels, including aspartate and alanine transaminases. Elevated transaminase levels may be associated with significant underlying liver disease and increased risk of liver-related and all-cause mortality. The most common causes of mildly elevated transaminase levels (two to five times the upper limit of normal) are metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease. Uncommon causes include drug-induced liver injury, chronic hepatitis B and C, and hereditary hemochromatosis. Rare causes are alpha₁-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic causes are celiac disease, hyperthyroidism, rhabdomyolysis, and pregnancy-associated liver disease. Initial laboratory testing assesses complete blood cell count with platelets, blood glucose, lipid profile, hepatitis B surface antigen, hepatitis C antibody, serum albumin, iron, total iron-binding capacity, and ferritin. If MASLD is suspected, the FIB-4 Index Score or NAFLD Fibrosis Score can be used to predict which patients are at risk for fibrosis and may benefit from further testing or referral to a hepatologist. All patients with elevated transaminases should be counseled about moderation or cessation of alcohol use, weight loss, and avoidance of hepatotoxic drugs.