Hepatitis B virus (HBV) infection is a globally distributed health problem. The number of carriers of HBV is estimated to exceed 240 million people worldwide. Compared with uninfected individuals, HBV carriers have an increased risk of developing hepatocellular carcinoma. The prevention of HBV infection is therefore strongly recommended, and a HBV vaccine is available. For carriers, treatment with nucleoside/nucleotide reverse transcriptase inhibitors is available, but infection frequently requires chronic treatment via a lifetime of medication. Thus, curing HBV infection remains a major challenge. However, despite the development of an infectious HBV cell culture system and recent intense research, many aspects of the HBV life cycle remain poorly characterized. In this review, we focus on the current understanding of the HBV life cycle and involved host factors, as well as potential targets for therapeutic intervention against HBV. We also consider possible immunotherapeutic strategies for eliminating HBV, including the removal of cccDNA from infected hepatocytes.