Governance is thought to be a key determinant of economic growth, social advancement and overall development, as well as for the attainment of the MDGs in low- and middle-income countries. Governance of the health system is the least well-understood aspect of health systems. A framework for assessing health system governance (HSG) at national and sub-national levels is presented, which has been applied in countries of the Eastern Mediterranean. In developing the HSG framework key issues considered included the role of the state vs. the market; role of the ministries of health vs. other state ministries; role of actors in governance; static vs. dynamic health systems; and health reform vs. human rights-based approach to health. Four existing frameworks were considered: World Health Organization's (WHO) domains of stewardship; Pan American Health Organization's (PAHO) essential public health functions; World Bank's six basic aspects of governance; and United Nations Development Programme (UNDP) principles of good governance. The proposed HSG assessment framework includes the following 10 principles-strategic vision, participation and consensus orientation, rule of law, transparency, responsiveness, equity and inclusiveness, effectiveness and efficiency, accountability, intelligence and information, and ethics. The framework permits 'diagnoses of the ills' in HSG at the policy and operational levels and points to interventions for its improvement. In the case of Pakistan, where the framework was applied, a positive aspect was the growing participation and consensus orientation among stakeholders, while weaknesses were identified in relation to strategic vision, accountability, transparency, effectiveness and efficiency and rule of law. In using the HSG framework it needs to be recognized that the principles are value driven and not normative and are to be seen in the social and political context; and the framework relies on a qualitative approach and does not follow a scoring or ranking system. It does not directly address aid effectiveness but provides insight on the ability to utilize external resources and has the ability to include the effect of global health governance on national HSG as the subject itself gets better crystallized. The improved performance of the ministries of health and state health departments is at the heart of this framework. The framework helps raise the level of awareness among policymakers of the importance of HSG. The road to good governance in health is long and uneven. Assessing HSG is only the first step; the challenge that remains is to carry out effective governance in vastly different institutional contexts.