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This chapter presents challenges and opportunities in the protection and preservation of indigenous knowledge (IK) in Africa. Specific examples have been taken from the Maasai pastoralists and the Sambaa and Zigua traditional medicine men of North-eastern Tanzania. The chapter argues that there is a threat of IK extinction due to lack of recording and problems associated with preservation and protection of the knowledge from pirates. Examples of efforts made by Tanzania in IK preservation, including efforts by the Economic and Social Research Foundation in developing IK database and training initiatives at the University of Dar es Salaam, are discussed. Ethical issues in IK systems are also discussed, with emphasis on returning IK benefits to the owners of the knowledge, and involving people in IK research. Finally, the chapter highlights challenges in IK prevention and suggests measures that can be taken to alleviate them. These include, among other things, developing appropriate IK policies and practices, establishing IK resource centres, offering training, doing research and developing South-South IK networks.