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Chronic <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> infection increases the risk of liver cirrhosis and hepatocellular carcinoma. To date, two classes of antiviral drugs have been approved by the <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>ood and <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>rug <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>dministration for the treatment of hepatitis <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, immunomodulators (interferon [<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>]\u2010\u03b1 and pegylated\u2010interferon [<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>]\u2010\u03b1) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [<jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>], and entecavir [<jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>]). Of these, <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TDF<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b1 are the most effective and are currently recommended for anti\u2010<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> therapy. However, these therapies are less than optimal because of their low rate of viral <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> and surface antigen clearance; thus, there exists a significant unmet medical need for safe and efficacious new anti\u2010<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> drugs. Covering diverse chemical structures and mechanisms of action, non\u2010nucleos(t)ide compounds offer great promise in the search for new anti\u2010<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> drugs. This review summarizes the currently approved anti\u2010<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> drugs and highlights advances in the identification and characterization of novel small molecule <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> inhibitors. 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