Different aspects of personal relationships including social integration, social support, and social conflict have been related to inflammation. This article summarizes evidence linking the quality and quantity of relationships with gene expression, intracellular signaling mechanisms, and inflammatory biomarkers, and highlights the biological and psychological pathways through which close relationships impact inflammatory responses. Relationship conflict and lower social support can effectively modulate proinflammatory cytokine secretion both directly (via CNS/neural/endocrine/immune biobehavioral pathways), and indirectly, by promoting depression, emotional stress responses, and detrimental health behaviors. Accordingly, thorough assessments of health behaviors and attention to key methodological issues are necessary to identify the contributions of relationships to inflammation, and thus we highlight procedural issues to be considered in the design of studies. Despite some notable methodological challenges, the evidence suggests that learning more about how close relationships influence inflammation will provide important new insights into the ways that relationships impact health.