Chronic hepatitis B (CHB) is a worldwide public health problem which carries an enormous economic andsocial burden.Convincing evidences show that persistent active viral replication is an independent predicatorfor disease progression.Therefore,suppressing HBV replication in a sustained manner is the cornerstone toprevent disease prog ression and prolong the su rvival of patients with CHB.Pivotal clinical trials and real-worldstudies show that nucleos(t)ide analogs (Nas) are very potent in terms of suppression of HBV DNA replicationand with very good safety profiles even in cirrhotic patients with or without decompensation.Although l-yeartreatment with Nas achieves only a modest rate of HBeAg seroconversion,extended treatment could increasethis rate.Profound suppression of HBV DNA can be translated into histologic improvement and clinical benefitin terms of decreasing disease progression in compensated or decompensated cirrhosis.It is critical to startwith a high potent and less resistant therapy to provide sustained long-term suppression of viral replication.Roadmap-approach may offer an alternative solution in which an inexpensive antiviral drug is started andanother drug is added-on or switched-to if there is a suboptimal on-treatment HBV DNA declining.In summary,high antiviral efficacy,excellent tolerability,wide applicability and well-proven histological improvement andlong-term clinical benefit all make Nas are preferred choice in most situations for the management of CHB with cirrhosis.