OBJECTIVE: There has been substantial research and public interest in mindfulness interventions, biological pathways, and health for the past two decades. This article reviews recent developments in understanding relationships between mindfulness interventions and physical health. METHODS: A selective review was conducted with the goal of synthesizing conceptual and empirical relationships between mindfulness interventions and physical health outcomes. RESULTS: Initial randomized controlled trials in this area suggest that mindfulness interventions can improve pain management outcomes among chronic pain populations, and there is preliminary evidence for mindfulness interventions improving specific stress-related disease outcomes in some patient populations (i.e., clinical colds, psoriasis, irritable bowel syndrome, posttraumatic stress disorder, diabetes, HIV). We offer a stress-buffering framework for the observed beneficial effects of mindfulness interventions and summarize supporting biobehavioral and neuroimaging studies that provide plausible mechanistic pathways linking mindfulness interventions with positive physical health outcomes. CONCLUSIONS: We conclude with new opportunities for research and clinical implementations to consider in the next two decades.