The Commission on Social Determinants of Health (the Commission) was launched by the World Health Organization in 2005. It aims to support countries and global health partners to act on social factors leading to ill-health and health inequalities. Taking action on the social determinants of health is not new for Australia. This paper provides a description of the work of the first 18 months of the Commission and relevant Australian examples. Taking action on the social determinants of health is never simple or easy even in the most supportive of policy environments. The global focus of the Commission should ensure that knowledge and examples of successful action will be collected from a diverse range of country and policy environments, particularly low to middle-income countries. Given Australia's experience, we encourage practitioners to contribute to the deliberations of the Commission. It is also critical that Australian practitioners engage with the Commission's different actors and stakeholders, particularly knowledge networks, to derive important policy lessons from the knowledge generated by the Commission.