With the development of new drugs, there has been a significant progression in the treatment of viral hepatitis B over the past five years. Based on their effect mechanisms, the currently available seven different drugs can be classified either as those of the interferon group or those of the nucleoside analogue group. Despite the pharmacological advances, it is still rare to achieve sustained response. The chances of a long-term inactive hepatitis stage, however, have greatly increased with the growing opportunities for personalized pharmacological treatment based on the selection of the correct type of drug, the timely modification of therapy in case of ineffectiveness and the determination of the optimal time and length of the therapy. For this, it is necessary to monitor several predictive, non-invasive biomarkers. For the initiation of the therapy, the most important markers are HBeAg, alanine-aminotranferase and HBV DNA serum levels and the viral genotype. During therapy, quantitative monitoring of the HBV DNA and HbsAg levels helps most to differentiate between those who will respond fast, those who will need longer treatment and those who are unlikely to respond and therefore need alternative drug therapy. A rapid decrease in or disappearance of HBsAg is predictive of successful response during interferon therapy, while changes in the HBV DNA level are more informative during treatment with nucleoside analogues. It is expected that information on the effects of combination therapy will become available soon and this may alter both the currently recommended treatment and monitoring strategy.