The discovery and development of novel, biologically active agents from natural sources, whether they be drugs, agrochemicals or other bioactive entities, involve a high level of interdisciplinary as well as international collaboration. Such collaboration, particularly at the international level, requires the careful negotiation of collaborative agreements protecting the rights of all parties, with special attention being paid to the rights of host (source) country governments, communities and scientific organizations. While many biodiversity-rich source countries currently might not have the necessary resources for in-country drug discovery and advanced development, they provide valuable opportunities for collaboration in this endeavor with research organizations from more high-income nations. This chapter discusses the experiences of the US National Cancer Institute and the US government-sponsored International Cooperative Biodiversity Groups program in the establishment of international agreements in the context of the Convention of Biological Diversity's objectives of promoting fair and equitable collaboration with multiple parties in many countries, and includes some specific lessons of value in developing such collaborations.