ABSTRACT: Chronic hepatitis B constitutes a significant health and economic burden to Asian countries. Six medications are now approved for the treatment of chronic hepatitis B, but there is still significant uncertainty with regards to treatment outcomes, cost impact, and benefits in view of the absence of long-term outcomes data. Cost-effectiveness Markov modeling thus allows us to project and estimate long-term outcomes based on current data and compare the cost-benefit between different treatment options. However, there are limitations to these reported studies. Cost-utility indices such as cost/quality-adjusted life years (cost/QALY) may not be intuitive to clinicians and patients. These studies are also usually based on first-world economies, using a benchmark of US$50,000/QALY, and cannot be extrapolated directly to Asia-Pacific countries. Cost-effectiveness of various treatment strategies using a combination of cost-effectiveness indices may provide a more complete picture. These include cost/HBeAg seroconversion for HBeAg-positive patients (range: US$19,400-30,800) and cost/HBV DNA negative (PCR assay) for HBeAg-negative patients (range: US$14,400-32,000) over 5-year time horizon; cost per cirrhosis prevented (range: US$326,000-686,000) and cost per HCC prevented (range: US$654,000-1,380,000) over 10-year horizon using data from REVEAL study, cost per end point complication prevented in cirrhotics (US$9,630/year), and cost per HCC prevented in cirrhotics (US$ 27,600/year) over a 32-month horizon, using data from Asia Lamivudine Cirrhosis Study. More potent antivirals with low resistance appear to have lower cost/clinical end point averted. Published reports of cost-utility analysis comparing treatment using conventional cost/QALY show that all treatment modalities fall below the first-world benchmark of US$50,000/QALY but vary in modeling assumptions and in quality, making comparisons difficult. Reimbursement policies affect out-of-pocket expenses to the patient, and increases the proportion of patients who can afford therapy, but generally do not affect cost-effectiveness. In conclusion, cost-effectiveness analysis is an important tool for health care administrators, clinicians, and patients to decide on the optimal therapy for chronic hepatitis B, but the methodology permits considerable leeway for interpretation of results, thus a combination of cost-effective indices may be needed to paint a more complete picture.