Overview of the HBV infection and replication cycle. Infecting virion particles are transported to the hepatocyte nucleus to release the relaxed circular partially double-stranded DNA genome, associated with the viral polymerase, into the nucleus. The genome is repaired and converted into cccDNA, which is the template for viral mRNA synthesis. The viral transcripts are translated following transport to the cytoplasm. The three surface antigen proteins are membrane specific and compose the viral envelope in conjunction with host lipid. Within the cytoplasm, pregenomic RNA (pgRNA) is encapsidated together with newly expressed polymerase protein within spontaneously formed capsid particles composed of core protein, to form the viral replication complex. pgRNA also serves as the template for the expression of the polymerase and core proteins. The HBV biomarkers discussed in this review, other than qAHBc, which is produced following the humoral immune response to core antigen, are shown within their expression pathways and their component parts. Note that HBsAg is detectable from replicative and non-replicative virion particles, as well as subviral particles and HBsAg expressed from HBV DNA integrated into host genomic DNA.