Telbivudine (Sebivo®; Tyzeka®) is a synthetic nucleoside analogue that inhibits replication of hepatitis B virus (HBV). It is used in the treatment of adults with chronic hepatitis B (CHB) with evidence of viral replication and persistently elevated serum ALT and/or AST levels, and/or histological evidence of active disease. Telbivudine is a potent antiviral that provides effective and sustained viral suppression in patients with compensated CHB. In clinical trials, treatment outcomes were improved significantly more with telbivudine 600 mg once daily than with lamivudine 100 mg or adefovir 10 mg once daily, and telbivudine-treated patients had significantly less viral resistance than lamivudine-treated patients. Increasing rates of hepatitis B e antigen (HBeAg) seroconversion were achieved in HBeAg-positive patients during periods of up to 4 years continuous telbivudine treatment, and seroconversion was durable in most patients throughout a 2-year, off-treatment follow-up, indicating the potential for a finite treatment period in this group of patients. Telbivudine is associated with a medium genetic barrier to resistance and, as patients with undetectable HBV DNA levels have significantly improved outcomes, it is recommended that HBV DNA levels are monitored at week 24 (and 6 monthly thereafter), with the addition of a nucleoside/nucleotide analogue without cross resistance (such as adefovir dipivoxil) if viraemia is present to reduce the risk of resistance (Roadmap concept). Telbivudine was generally well tolerated in clinical trials for periods of up to 4 years, and has a similar tolerability profile to that of lamivudine. A minority of telbivudine-treated patients experience creatinine kinase elevation, usually transient, and myopathy occurs rarely. In modelled cost effectiveness studies in several Asian countries, treatment with telbivudine Roadmap was cost effective in HBeAg-positive patients. Thus, telbivudine provides a valuable treatment option in CHB, particularly when administered using the Roadmap concept in HbeAg-positive patients.