The 'macro-structural' determinants of health, which include macroeconomic policy and social policy, significantly influence people's living and working conditions, behaviours, and health. Trade policy is one example of a macro-structural determinant, with increasingly well recognised health outcomes. The health effects of macro-structural determinants such as trade policy are mediated through the policy and governance mechanisms of economic, social, and political institutions. Thus, responding to these determinants will require actions that generate institutional and policy changeand a politically-informed research approach. Some recent empirical work in the public and global health community has taken a more politically-informed approach to trade and health, however there is scope for considerable conceptual and methodological development. We describe how a perspective informed by political science might inform new ways of investigating and addressing trade policy to improve health outcomes. A range of theories and methods from policy studies are relevant, but particularly important will be application of institutional and ideational lenses of policy analysis, to understand better policy processes and inform avenues for macrostructural change.