There is a growing interest in the application of mindfulness techniques for modulating one’s relationship to ongoing mental experience. However, there is need for detailed empirical investigations using experimental paradigms to address (a) whether mindfulness training works, (b) how it affects emotional reactivity and regulation, (c) what neural systems are modulated by training in mindfulness techniques, and (d) how these might compare to cognitive regulatory strategies. This study examined the brain-behavior correlates of different methods of emotion regulation—mindfulness awareness, cognitive-linguistic, and attentional distraction—in adult social phobics (SP), and the neural mechanisms underlying therapeutic change associated with mindfulness meditation based stress reduction (MBSR) training. A multi-level assessment (questionnaires, autonomic psychophysiology, functional magnetic resonance imaging, clinical diagnostic interview) was administered before and after MBSR. Participants were presented with negative self-beliefs related to autobiographical social situations and then cued to shift into mindful awareness, cognitive restructuring, or attentional distraction during fMRI scanning with concurrent emotion rating and autonomic physiological measurements. At baseline, 15 SP were compared to 15 demographically-matched healthy controls (HC). Post-MBSR, SP treatment completers were compared to their own pre-MBSR measurements. At baseline, compared to HC, SP demonstrated (a) greater emotional reactivity to negative self-beliefs in emotion ratings and left amygdala, (b) less effective cognitive regulation of emotion, but (c) equivalent efficacy for cognitive regulation and mindful awareness compared to attentional distraction in reducing emotional reactivity. Compared to baseline, at post-MBSR, SP showed significant (a) decreased social anxiety, state anxiety, emotional reactivity (b) increased self-esteem, (c) enhanced neural activity in attentional networks during mindful awareness. These results suggest (a) differential effectiveness of various emotion regulation techniques in SP and HC, and (b) highlight the role of attention as a potential mechanism for MBSR related changes in adults with social anxiety.