Asia comprises more than 40 countries encompassing a wide geographic area with a very large population. Many of these countries have low-income economies together with high endemicity of chronic hepatitis B virus (HBV) infection, which is usually acquired perinatally or during early childhood. The well elucidated natural history of chronic HBV infection, together with the extensive research and the longest experience in the use of therapeutic agents in Asia have provided a great opportunity for Asian patients to benefit from recent advancements. However, treatment of chronic HBV infection is a complex task that requires individualized assessment, thus representing a great challenge for general physicians. The inherent problems of the drugs currently available, together with a lack of awareness of the disease among patients, government, and healthcare practitioners are obstacles to proper management of HBV. The most critical challenge and obstacle is the high cost of medical care and antiviral drugs. Lack of adequate reimbursement for treatment and diagnostic testing makes adherence to treatment guidelines impossible. Hence lamivudine is still widely used in Asia. To address these challenges, the ongoing awareness campaigns, active screening programs, educational activities are needed but must be enhanced. Cost-cutting measures and international support are essential to improve the difficult situation in this part of the world.