Hepatitis B virus (HBV) evades, subverts, activates and regulates host immune components, thereby impacting its natural history and disease pathogenesis. Recent advances in our understanding of immune interactions in chronic viral infection and tumor therapy are applicable to chronic hepatitis B (CHB). With recent successes of tumor immunotherapy, there is a renewed interest in exploring immunotherapeutics in achieving sustained and functional cure of chronic hepatitis B. In this review, we discuss aspects of host innate and adaptive immune regulatory and pathogenic responses relevant for HBV infection. We also highlight several immune modulatory approaches in clinical development to treat CHB.