There has been much progress in antiviral therapy for chronic hepatitis B; however, antiviral therapy for hepatitis B in special populations is still very challenging. Here, we review antiviral therapy for hepatitis B in special populations, including children and pregnant patients, patients with hepatitis-B-related cirrhosis, patients with acute hepatitis B and chronic hepatitis B surface antigen carriers who receive immunosuppressive or cytotoxic therapy. Major advances have been made in antiviral therapy for hepatitis B in these special populations because of recent increasing availability of oral nucleoside/nucleotide analogues that are well-tolerated and highly effective; however, the findings are mostly based on small uncontrolled short-term studies. More well-designed clinical studies on antiviral therapy for hepatitis B in these special populations are urgently needed to obtain more evidence-based high-quality data.