OBJECTIVES The pharmacovigilance guidances have been implemented in many well developed countries, but in the developing countries it remains largely unclear. The purpose of this study was to review the current status of post-marketing drug safety surveillance in developing countries as defined by low and lower-middle-income economies and to compare it with some of the developed countries as defined by high-income economies. METHODS Using Pubmed, EMBASE, Cochrane, textbooks, and Internet search engines, an extensive literature review on post-marketing drug safety surveillance systems were reviewed in terms of regulatory policy, organizational structure, adverse drug reaction (ADR) reports, and safety monitoring system. The available data in the developing countries namely India, Zambia, Tanzania, China, Cuba, Ukraine, Malaysia, Chile and South Africa were then compared with that in the developed countries namely Netherlands, United Kingdom, and the United States. RESULTS Some developing countries like China and India are establishing pharmacovigilance centers and appear to be actively involved in post marketing surveillance. A handful of developing countries have a well planned strategy for pharmacovigilance. Many countries such as Kenya and Ethiopia do not have an ADR reporting system. Paucity of trained and experienced personnel, financial resources, and availability and irrational use of herbal medicines are some of the major obstacles in planning a well organized and structured ADR reporting system. The developing countries also lack well defined guidelines on risk management. CONCLUSIONS There is a definite need for drug safety programs in the developing countries given the fact that these countries differ markedly in terms of type of disease prevalence, patient genotype and environment. A cooperative and exhaustive effort by the regulatory authorities, physicians, as well as the pharmaceutical industry will be needed in order to create a functioning pharmacovigilance system in these countries.