BACKGROUND: Mindfulness meditation (MM) practices constitute an important group of meditative practices that have received growing attention. The aim of the present paper was to systematically review current evidence on the neurobiological changes and clinical benefits related to MM practice in psychiatric disorders, in physical illnesses and in healthy subjects. METHOD: A literature search was undertaken using Medline, ISI Web of Knowledge, the Cochrane collaboration database and references of retrieved articles. Controlled and cross-sectional studies with controls published in English up to November 2008 were included. RESULTS: Electroencephalographic (EEG) studies have revealed a significant increase in alpha and theta activity during meditation. Neuroimaging studies showed that MM practice activates the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC) and that long-term meditation practice is associated with an enhancement of cerebral areas related to attention. From a clinical viewpoint, Mindfulness-Based Stress Reduction (MBSR) has shown efficacy for many psychiatric and physical conditions and also for healthy subjects, Mindfulness-Based Cognitive Therapy (MBCT) is mainly efficacious in reducing relapses of depression in patients with three or more episodes, Zen meditation significantly reduces blood pressure and Vipassana meditation shows efficacy in reducing alcohol and substance abuse in prisoners. However, given the low-quality designs of current studies it is difficult to establish whether clinical outcomes are due to specific or non-specific effects of MM. DISCUSSION: Despite encouraging findings, several limitations affect current studies. Suggestions are given for future research based on better designed methodology and for future directions of investigation.