Conventional approaches for the prevention and control of communicable diseases within Indigenous contexts may benefit from new insights arising from the growing interest in syndemics. Syndemics is a term used to describe a conceptual framework for understanding diseases or health conditions, and how these are exacerbated by the social, economic, environmental and political milieu in which a population is immersed. The use of conventional approaches for outbreak prevention and control remains the bedrock of intervention in the field of communicable diseases; yet on their own, these strategies are not always successful, especially within contexts of marginalization and disadvantage. A broader approach is needed; one that examines the systemic factors involved, understands how various policies and systems support or hinder effective responses and identifies the structural changes needed to create more supportive environments and increase the resilience of the population. In an Indigenous context, whether the focus is on hepatitis C, tuberculosis, HIV or water-borne diseases, it is important to recognize that a) social determinants contribute to the emergence and persistence of outbreaks, b) conventional approaches to communicable disease control are necessary but not sufficient, and c) using a "syndemics lens" can leverage action at multiple levels to tackle the root causes of poor health and inform more effective strategies for improving Indigenous health and reducing health inequities.