Entecavir monotherapy has now been evaluated in patients with hepatitis B virus (HBV)-related decompensated cirrhosis. Entecavir achieves 1-year HBV DNA undetectability rates in up to 90% of treatment-naive patients in this setting without any case of resistance. Entecavir was generally safe and well tolerated. Lactic acidosis was described almost exclusively in very advanced liver disease (MELD score >20) and usually subsided with drug discontinuation. After 1 year of entecavir therapy, the Child–Pugh score improved by ≥2 points in up to 50% of patients and decreased mean MELD score by >2 points. The 1-year survival rates were 84–91%, mainly associated with baseline Child–Pugh or MELD scores. In conclusion, entecavir monotherapy is an excellent treatment option for treatment-naive patients with HBV-related decompensated cirrhosis.