The first priority in the treatment of chronic hepatitis B (hereafter referred to as hepatitis B) is to suppress the virus, but the long course of antiviral therapy and the high cost make a considerable number of hepatitis B patients apprehensive. Therefore, it is especially important to choose the right time for antiviral treatment. So, what is the most appropriate timing for antiviral therapy after hepatitis B virus infection? What is the most appropriate timing for antiviral therapy after hepatitis B virus infection to achieve effective and durable viral suppression to delay and stop disease progression? In fact, not all patients with hepatitis B need antiviral therapy. HBsAg positive patients, regardless of HBV DNA level, such as normal liver function such as transaminases, and liver histological examination does not reveal obvious inflammatory necrosis, then these patients do not need to be treated with antiviral therapy. The blind use of antiviral drugs at this time will increase the patient’s financial burden but may not be able to achieve the desired effect of suppressing the virus. Conversely, if a patient with hepatitis B has elevated transaminases or liver histology suggesting inflammatory necrosis and fibrotic lesions in the liver, then an appropriate drug can be considered to start antiviral therapy. In some special populations with HBV-DNA positivity, antiviral therapy should be considered even if the above treatment criteria are not met. For example, hepatitis B patients older than 40 years old with ALT greater than the upper limit of normal can be considered for antiviral therapy; while those over 40 years old with persistently normal ALT should be followed closely, preferably with liver biopsy, and if liver histology shows more than moderate inflammatory necrosis or fibrosis, antiviral therapy should be actively administered. Another dynamic observation reveals evidence of disease progression (e.g., enlarged spleen), liver histology is recommended, and antiviral therapy should be given if necessary. As can be seen, the timing of antiviral therapy has both commonalities and individual differences, as does the selection of antiviral drugs. It is worth noting that when a patient with hepatitis B first presents with an ALT level 2 times the upper limit of normal, the body may be undergoing an active viral clearance with the opportunity for long-term suppression of the hepatitis B virus through the autoimmune system; therefore, in the absence of a background of cirrhosis and a trend toward liver failure, close dynamic monitoring of liver function and changes in HBV DNA and withholding of antiviral drugs is feasible. Once the ALT has been repeatedly elevated for more than 3 months, antiviral therapy is imperative.