Abstract Liver transplantation remains the ultimate cure for patients with hepatitis B virus-related end-stage liver disease. Clinical Practice Guidelines currently recommend that patients with decompensated HBV cirrhosis should be treated without delay with nucleos(t)ide analogues regardless of the patient's serum ALT, HBV DNA level, and HBeAg status. The main goal of pre-transplantation antiviral therapy is to achieve a rapid and prolonged suppression of viral replication and thus decrease the risk of hepatitis B virus reinfection of the graft. In addition, sustained negativization of serum HBV DNA may also result in clinical stabilization which can decrease the mortality rate while on the waiting list and delay or avoid liver transplantation in some cases. Clinical improvement may take from 3 to 6 months to become evident. Lamivudine and adefovir are no longer considered first-line therapy in these patients. Potent nucleos(t)ide analogues with good resistance profiles such as entecavir or tenofovir should be used instead. Preliminary data suggest that these agents are effective and have a good safety profile in patients with decompensated cirrhosis. More safety data, however, are needed, particularly in patients with severe impairment of liver function. More data are needed to determine which of the newer antiviral agents offer the best risk–benefit ratio in this challenging patient population. Although a tenofovir-based regimen may be preferred in decompensated patients with lamivudine-resistant hepatitis B virus, there are some concerns about the long-term safety of tenofovir including nephrotoxicity and metabolic bone disease.