Major depressive disorder (MDD) is highly burdensome and psychological and biological features are mechanistically implicated in its etiology. Fewer than one-in-three depressed patients achieve remission after treatment. Understanding treatment mechanisms of MDD is clearly an important objective. Mindfulness training emphasizes the development of attention and experiential acceptance, improves depressive symptoms, reduces the likelihood of relapse, and is as effective as frontline treatments. Mindfulness holds promise in psychiatry, in part, because it is highly personalizable and applicable to transdiagnostic factors. In spite of this promise, the mechanisms of mindfulness for MDD are unknown. Understanding mechanisms of mindfulness for MDD promises to inform biomarkers and tailored treatments and thus to contribute to reducing the massive burden of MDD and related conditions. We will conduct a randomized controlled trial to assess the impact of mindfulness training on behavior, biology (including the brain and physiology), and psychology (including cognition and affect), and thereby advance a mechanistic model of mindfulness training for MDD.