The treatment of traditional knowledge (TK) and plant genetic resources is timely international topics for debate with the focus on preventing the misappropriation and misuse of these resources, and on promoting the equitable sharing of benefits that arise from utilization and commercialization. In this paper, the initiatives of the Association of Southeast Asian Nations (ASEAN) and its member countries toward safeguarding TK associated with plant genetic resources are reviewed. While Malaysia, Thailand and the Philippines have national frameworks in place for the protection of TK and plant genetic resources, other ASEAN member countries do not. In addition, true regional cooperation among ASEAN countries in the area of TK and plant genetic resources has yet to be realized. After a review of these cases, this paper will argue that a single unique model or solution for all ASEAN member countries cannot meet the wide range of concerns and objectives that exist to protect TK and plant genetic resources. Instead, what is suggested is to create a mix of solutions to better handle TK and plant genetic resources issues.