Resmetirom achieved a historic milestone as the first drug to simultaneously resolve metabolic dysfunction-associated steatohepatitis (MASH) and improve liver fibrosis, earning FDA approval in 2024. This selective thyroid hormone receptor-β agonist works by mimicking T3 hormone specifically in liver tissue, reducing intrahepatic fat accumulation without systemic thyroid effects. Clinical trials demonstrated efficacy in patients with fibrotic MASH, measured by liver stiffness values of 10-20 kPa. This approval represents a paradigm shift for the estimated one-third of adults worldwide with metabolic dysfunction-associated steatotic liver disease, particularly those with obesity or diabetes where 10-30% progress to dangerous fibrosis. The liver-selective mechanism offers a sophisticated approach to metabolic liver disease, addressing both inflammation and scarring simultaneously. However, real-world implementation faces complex positioning challenges, especially with semaglutide also gaining MASH approval. The optimal sequencing of these therapies, potential combination strategies, and long-term cardiovascular outcomes remain unresolved. Early adoption data shows promise, but the true measure of resmetirom's impact will depend on how effectively clinicians integrate this liver-specific hormonal approach into comprehensive metabolic care strategies.