The article discusses the recent FDA conditional approval of resmetirom, a liver-targeted thyroid hormone receptor-β selective drug, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis. Resmetirom has shown promise in clinical trials by reducing hepatic fat content, improving liver histology, and ameliorating biomarkers of liver damage without significant effects on body weight. The authors highlight the significance of resmetirom in addressing the growing global health challenge posed by metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of adults worldwide and is linked to increased mortality rates and substantial healthcare costs. The article also reviews the preclinical data, clinical impact, safety profile, and clinical implementation of resmetirom, emphasizing its potential to revolutionize the treatment of MASH and MASLD. Additionally, it discusses the future research directions and challenges, including the need for long-term safety and efficacy studies, and the potential for combination therapy with other hepatoprotective agents.The article discusses the recent FDA conditional approval of resmetirom, a liver-targeted thyroid hormone receptor-β selective drug, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis. Resmetirom has shown promise in clinical trials by reducing hepatic fat content, improving liver histology, and ameliorating biomarkers of liver damage without significant effects on body weight. The authors highlight the significance of resmetirom in addressing the growing global health challenge posed by metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of adults worldwide and is linked to increased mortality rates and substantial healthcare costs. The article also reviews the preclinical data, clinical impact, safety profile, and clinical implementation of resmetirom, emphasizing its potential to revolutionize the treatment of MASH and MASLD. Additionally, it discusses the future research directions and challenges, including the need for long-term safety and efficacy studies, and the potential for combination therapy with other hepatoprotective agents.