Since active replication of hepatitis B virus is strongly associated with the development of cirrhosis, hepatocellular carcinoma, and liver-related mortality, antiviral therapy is aimed at maximal viral suppression. However, as no antiviral therapy is perfect due to the emergence of resistant strains and suboptimal efficacy in some patients, modifying the treatment strategies for certain patients in advance is important through prediction of treatment responses. Recently, along with serial monitoring of hepatitis B virus DNA level, quantitative analysis of the serologic markers HBsAg (qHBsAg) and HBeAg (qHBeAg) has been used to predict responses to antiviral therapy. The clinical usefulness of both pretreatment qHBsAg and decline in qHBsAg during treatment was assessed in patients treated with pegylated interferon, suggesting that they might be used as another criterion to identify good and poor responders. Similarly, in patients treated with oral nucleos(t)ide analogues (NAs), the clinical significance of qHBsAg has been reported in some studies. However, as the decline in qHBsAg is much slower during NA therapy and the data on the use of qHBsAg to predict response to NA treatment are very preliminary, its wide application remains to be determined. Another serologic marker (qHBeAg) measured at baseline and during treatment might be applied for identifying good or poor responders to antiviral therapy. Unfortunately, measurement of qHBeAg has not been widely used because it is expensive, nonstandardized, and unavailable in patients with HBeAg-negative chronic hepatitis B (CHB). In conclusion, serologic markers may be potential predictors of response to antiviral therapy in CHB, allowing delivery of the most appropriate treatments to the most suitable patients. Further investigations into the universal clinical usefulness of such markers are needed.