Liver transplantation has revolutionized treatment for end-stage liver disease and select malignancies, offering curative therapy for patients with otherwise fatal conditions. This review examines the major indications for liver transplantation across four primary categories: acute liver failure, complications of decompensated cirrhosis, metabolic liver diseases, and systemic complications of chronic liver disease and touches on oncologic indications for transplantation. Among these indications, acute liver failure demands the most urgent intervention, requiring immediate transplant center referral due to its unpredictable progression and high mortality without transplantation. In contrast, cirrhosis requires consideration of transplantation at the time of decompensation manifesting with the onset of ascites, variceal bleeding, and hepatic encephalopathy. Additionally, metabolic disorders, including Wilson disease and inborn errors of metabolism, may present as acute liver failure requiring urgent recognition and rapid transplant evaluation. Beyond these primary indications, oncologic conditions represent an expanding transplant indication, including hepatocellular carcinoma, hilar and intrahepatic cholangiocarcinoma, and metastatic colorectal cancer. Understanding these diverse indications and their distinct clinical trajectories is essential for optimal patient care and timely transplant referral.