National registries are databases intended to collect data useful for better planning and regulation of healthcare delivery at a national level. National registries can help government officials, health practitioners, and clinical researchers answer a variety of critical questions. These questions can be related to the efficacy of new drugs, spread patterns of a particular disease, or risk factors of certain sub-groups. Construction of health registries in developing countries has been considered a challenging process as evidenced by the lack of such necessary registries in a number of countries and the failure of registry projects in some others. This paper attempts to provide a methodical approach for understanding the main challenges that face national registry projects in developing countries. The main issues are discussed and, whenever is appropriate, suggestions for handling these issues and are provided together with practical examples to support the presented arguments.