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In this article, the author briefly examines various definitions of ‘global health diplomacy’ (GHD), reviews possible fundamental principles and discusses unresolved challenges. He argues that fundamental principles of GHD should include: ethical participation and decision making; human rights concerns and enforcements; rule of law and clear process for settling disputes; social determinants of health and how to mitigate their impact; shared bilateral and international interests and priorities; centrality of target populations and sensitivities to local customs, religions and social mores; research as part of efforts to expand the frontiers of the field; training and field experience for all practitioners; an understanding of political, policy making, advocacy and implementation issues in global health; globalisation and international trade issues; integration and mainstreaming of policies and programmes in the relationship between global health, bilateral diplomacy and multilateral development; and public/private/civil society partnerships and alliances. He identifies five challenges for GHD. The first challenge is to further develop the field of GHD as a discipline. The second challenge is how to harmonise the divergent orientation of public health experts, trained diplomats and development experts. Thirdly, stakeholders must ensure that global health diplomacy retains a significant focus on the needs of target populations around the world. They should also ensure that global health diplomacy does not create additional tensions between donor and host nations. Finally, stakeholders must find strategies to maintain the current non-partisan support of policy makers on global health issues over the long term.