Epidemiological studies indicate that better marital quality is associated with less morbidity and premature mortality. A number of interpersonal processes related to marital quality are also associated with health-relevant surrogate biomarkers across different physiological systems. Despite these replicated correlational findings, few interventions have harnessed interpersonal processes as potential interventions to enhance health. Building on Dr. Janice Kiecolt-Glaser's model of relationships and health, we propose that couples-based health behavior change interventions may represent an effective way to decrease dysregulation across autonomic, endocrine and immune systems and, ultimately, improve dyadic health. Given that the cohabiting partner is an essential part of the social context in which the behavior change is being pursued, it is important to consider the relational issues triggered by dyadic interventions. Using a relationship science perspective, this article reviews the literature on couples' concordance in health behaviors and health outcomes, the potential pathways underlying this concordance, theories of the couple as a self-sustaining social system, dyadic adaptation of individual self-regulation strategies, effective and ineffective social support and social control in couple relationships, the integration of relationship-building and health behavior change strategies, and the consideration of key moderators related to the nature of the relationship and the context surrounding the relationship. These findings highlight the importance of adopting a relationship science perspective when designing and testing dyadic interventions to improve health outcomes. The data reviewed provide insights on how to optimize couples-based health behavior change interventions to reduce physiological dysregulation and improve dyadic health.