Interventions and research to address the US opioid crisis have, for the most part, targeted opioid use, misuse, and addiction specifically. While such a focus can lead to useful innovations in the care of opioid use disorder, the fact that many persons with opioid use disorder use multiple substances (both over their life course and simultaneously in drug-using episodes) makes it imperative to address broader issues of addiction in persons who have opioid use disorder as their presenting concern. Because of integrated care and the ability to target multiple clinical concerns in parallel, the Veterans Administration (VA) may be uniquely situated to address the key issue of multi-morbidity that persons with opioid use disorder so frequently exhibit. Research at the VA can build on new interventions developed by the National Institutes of Health (and others) and can help to determine the best ways to implement these interventions. Research at the VA does not need to duplicate efforts supported by other funders but can complement such work by providing an integrated platform for determining the best approaches to implementing innovations. The real-world learning health system that has been developed in the VA is poised to contribute in just such important ways.