Abstract: Long-term and persistent hepatitis B virus(HBV) infection may lead to severe complications such as liver cirrhosis and liver cancer. The overall objective of the treatment of the Chronic hepatitis B(CHB) patients is long-term inhibition of HBV replication, alleviation of liver damage, reduction of complications, and extension of survival time. At present, nucleos(t)ide analogues(Nas) and interferons(IFN) are the major drugs for antiviral therapy, however, some of the patients who receive long-term antiviral therapy still have low-level viremia(LLV). The LLV is closely associated with liver cancer and poor prognosis. The review focuses on the current status of antiviral treatment of the CHB patients and the incidence of LLV among the patients who are treated with oral administration of major antiviral drugs, further explores the high-risk factors, potential mechanisms and current management strategies for LLV so as to optimize the therapeutic regimen for long-term treatment of CHB and improve the quality of life.