Environment and development agendas are increasingly being characterised by regional-scale initiatives. This trend is in part motivated by recognition of the need to account for global drivers of change (e.g., climate change, migration, and globalisation), the aspirations of achieving large-scale ecological goals (such as maintaining ecosystem processes), and reconciling potentially conflicting priorities in multi-use planning. However, regional-scale governance is challenging and there is little theoretical guidance or empirical evidence to suggest how it can be achieved. This paper uses the Institutional Analysis and Development framework to highlight the diverse contextual factors that challenge governance of a large-scale marine common, using an example of the Coral Triangle Initiative. The analysis points to the need for a critical, reflexive approach to the Coral Triangle Initiative if it is to effectively navigate diverse contexts and reconcile multiple objectives in the region. Recognising the heterogeneous, multi-scale and interlinked nature of large-scale marine systems is critical. Coping with contextual complexity will require innovative approaches that strive to be inclusive of varied perspectives and actors, enable and support effective collective-choice arrangements at lower levels of organisation, and organise and link diverse institutional arrangements at multiple scales. Large-scale marine governance will also involve a great deal of experimentation and regular adjustments to governance arrangements to account for the dynamic nature of regional commons.