Despite large gains in health over the past few decades, the distribution of health risks worldwide remains extremely and unacceptably uneven. Although the health sector has a crucial role in addressing health inequalities, its efforts often come into conflict with powerful global actors in pursuit of other interests such as protection of national security, safeguarding of sovereignty, or economic goals. This is the starting point of The Lancet-University of Oslo Commission on Global Governance for Health. With globalisation, health inequity increasingly results from transnational activities that involve actors with different interests and degrees of power: states, transnational corporations, civil society, and others. The decisions, policies, and actions of such actors are, in turn, founded on global social norms. Their actions are not designed to harm health, but can have negative side-effects that create health inequities. The norms, policies, and practices that arise from global political interaction across all sectors that affect health are what we call global political determinants of health. The Commission argues that global political determinants that unfavourably affect the health of some groups of people relative to others are unfair, and that at least some harms could be avoided by improving how global governance works. There is an urgent need to understand how public health can be better protected and promoted in the realm of global governance, but this issue is a complex and politically sensitive one. Global governance processes involve the distribution of economic, intellectual, normative, and political resources, and to assess their effect on health requires an analysis of power. This report examines power disparities and dynamics across a range of policy areas that aff ect health and that require improved global governance: economic crises and austerity measures, knowledge and intellectual property, foreign investment treaties, food security, transnational corporate activity, irregular migration, and violent conflict. The case analyses show that in the contemporary global governance landscape, power asymmetries between actors with conflicting interests shape political determinants of health. We identified five dysfunctions of the global governance system that allow adverse eff ects of global political determinants of health to persist. First, participation and representation of some actors, such as civil society, health experts, and marginalised groups, are insufficient in decision-making processes (democratic deficit). Second, inadequate means to constrain power and poor transparency make it difficult to hold actors to account for their actions (weak accountability mechanisms). Third, norms, rules, and decision-making procedures are often impervious to changing needs and can sustain entrenched power disparities, with adverse eff ects on the distribution of health (institutional stickiness). Fourth, inadequate means exist at both national and global levels to protect health in global policy-making arenas outside of the health sector, such that health can be subordinated under other objectives (inadequate policy space for health). Lastly, in a range of policy-making areas, there is a total or near absence of international institutions (eg, treaties, funds, courts, and softer forms of regulation such as norms and guidelines) to protect and promote health (missing or nascent institutions). Recognising that major drivers of ill health lie beyond the control of national governments and, in many instances, also outside of the health sector, we assert that some of the root causes of health inequity must be addressed within global governance processes. For the continued success of the global health system, its initiatives must not be thwarted by political decisions in other arenas. Rather, global governance processes outside the health arena must be made to work better for health. The Commission calls for stronger cross-sectoral global action for health. We propose for consideration a Multistakeholder Platform on Governance for Health, which would serve as a policy forum to provide space for diverse stakeholders to frame issues, set agendas, examine and debate policies in the making that would have an eff ect on health and health equity, and identify barriers and propose solutions for concrete policy processes. Additionally, we call for the independent monitoring of how global governance processes aff ect health equity to be institutionalised through an Independent Scientific Monitoring Panel and mandated health equity impact assessments within international organisations. The Commission also calls for measures to better harness the global political determinants of health. We call for strengthened use of human rights instruments for health, such as the Special Rapporteurs, and stronger sanctions against a broader range of violations by nonstate actors through the international judicial system. We recognise that global governance for health must be rooted in commitments to global solidarity and shared responsibility through rights-based approaches and new frameworks for international financing that go beyond traditional development assistance, such as for research and social protection. We want to send a strong message to the international community and to all actors that exert influence in processes of global governance: we must no longer regard health only as a technical biomedical issue, but acknowledge the need for global cross-sectoral action and justice in our eff orts to address health inequity.