Mindfulness-based interventions are increasingly used in the treatment and prevention of mental health conditions. Despite this, the mechanisms of change for such interventions are only beginning to be understood, with a number of recent studies assessing changes in brain activity. The aim of this systematic review was to assess changes in brain functioning associated with manualised 8-session mindfulness interventions. Searches of PubMed and Scopus databases resulted in 39 papers, 7 of which were eligible for inclusion. The most consistent longitudinal effect observed was increased insular cortex activity following mindfulness-based interventions. In contrast to previous reviews, we did not find robust evidence for increased activity in specific prefrontal cortex sub-regions. These findings suggest that mindfulness interventions are associated with changes in functioning of the insula, plausibly impacting awareness of internal reactions ‘in-the-moment’. The studies reviewed here demonstrated a variety of effects across populations and tasks, pointing to the need for greater consistency in future study design.