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Initial well-controlled studies have suggested that mindfulness training interventions can improve a broad range of mental and physical health outcomes (e.g., HIV pathogenesis, depression relapse, inflammation, drug abuse), yet the underlying pathways linking mindfulness and health are poorly understood. In this article, we offer a mindfulness stress buffering account to explain these health outcomes, which posits that mindfulness-based health effects are mostly likely to be observed in high-stress populations for which stress is known to affect the onset or exacerbation of disease pathogenic processes. We then offer an evidence-based biological model of mindfulness, stress buffering, and health.