Hepatitis B virus (HBV) infection is regarded as a major health concern worldwide. In patients with chronic HBV infection, exhausted virus-specific CD8+ T cells, resulting from the activation of the programmed cell death protein 1 and programmed death ligand 1 axis, play a key role in the chronicity of infection. Functional cure for HBV, defined as the seroclearance of hepatitis B surface antigen (HBsAg), is viewed as the optimal goal of chronic HBV infection treatment because HBsAg loss is associated with a low risk of hepatocellular carcinoma and a relatively favorable prognosis. Both interferon treatment and finite antiviral therapy are associated with positive HBV outcomes. Overall, combining immune checkpoint inhibitors with nucleos(t)ide analogs appears to be a promising approach for achieving HBsAg loss, particularly in patients with low HBsAg levels.