Chronic infection with hepatitis B virus (HBV) is a global public health problem because of its worldwide distribution and its potential to cause sequelae. HBV is most prevalent in China, South East Asia, sub-Saharan Africa, and the Amazon basin of South America where health care resources are most limited. Numerous challenges exist for effective management of chronic HBV infection, particularly in resource-limited regions. These challenges include lack of accurate prevalence data, absence of a surveillance program, and poor political will of governments in resource-poor countries to enforce effective measures to control the disease. There is a lack of understanding regarding HBV infection by both the general public and health care providers. A better understanding of the pathogenesis and treatment of this condition is necessary The acute shortage of trained medical manpower necessary for accurate diagnosis and treatment of chronic hepatitis B (CHB) in resource-poor countries is a formidable challenge. The condition is complicated by the continuing efflux of medical graduates from low-income economies to richer countries. The most critical problem in the management of CHB is the high cost of laboratory tests and drugs. Drugs are also not readily available. Other challenges in the management of CHB include stigmatization of patients, co-infection with other viruses, lack of management guidelines, and absence of an effective patient referral system. To address these challenges, governments of resource-poor nations must be committed to budgetary allocation for the implementation of health programs. It is necessary to provide awareness campaigns, health education, proper screening of blood and blood products for transfusion, active screening, intensification of existing childhood immunization, technical and financial assistance from wealthier nations, and implementation of the recommendations outlined in the Global Hepatitis Policy (2010).