Hepatitis B is one of the most prevalent viral diseases in the world. It leads to chronic liver disease in 10% of infected individuals, putting them at an increased risk for liver-related morbidity and mortality from complications of cirrhosis and hepatocellular carcinoma. Despite the success of universal hepatitis B vaccination in many countries, this disease remains a major public health problem, resulting in more than 500,000 deaths per year. Although the current therapy for chronic hepatitis B (CHB) is effective, it is not optimal; novel approaches to the management of CHB are needed. An improved understanding of virus-host interactions, advances in gene therapy, the development of molecular therapies targeted at different stages of the hepatitis B virus life cycle, and new insights into various approaches of immune modulation will lead to the development of better therapeutic agents for the management of CHB. These advances herald a new era of combination therapy. In this review, we will discuss emerging therapies and potential mechanisms, and highlight the promises and pitfalls of these new treatment strategies.