This review investigates how recent neuroimaging findings on vulnerability for depression and the mechanisms of mindfulness may serve to inform and enhance the understanding that is guiding the use of mindfulness training in the prevention and treatment of recurrent and chronic depression. In particular, we review evidence suggesting that alterations in default-mode-network activity and connectivity represent a fundamental deficit underlying cognitive vulnerability for depression and explore the ways in which mindfulness meditation may reverse such alterations. Furthermore, we discuss findings from studies that have investigated the effects of mindfulness on emotion-regulatory capacities. These findings suggest mindful emotion regulation has a characteristic neural signature that is particularly conducive to therapeutic learning. We conclude that training in mindfulness has unique strengths for addressing neural mechanisms associated with cognitive vulnerabilities for recurrent and chronic depression and propose future lines of research to more effectively harness this potential.